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pmc-6306413-1
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The proband (III-1) was a 16 year old boy from a non-consanguineous family with healthy parents (Figure ). He presented with weakness of upper and lower limbs, as well as hand muscle atrophy at the age 10. His medical history was insignificant. In the following time, muscle atrophy gradually spread to the forearm, upper arm, shoulder and pelvic girdles, thigh, crus, and foot muscles. At age 16, he showed an ataxic gait, upper limb ataxia, occasional diplopia, slurred speech, and cognitive decline. Neurological examinations revealed clinical signs of cerebellar ataxia, brisk tendon reflexes, and Babinski signs in lower limbs (Table ). Muscle atrophy was mostly severe in the thenar muscles and interosseus muscles of hands (Figure ), and shoulder girdle muscle (Figure ). Bilateral pes cavus (Figure ) and mild ankle arthrogryposis were found. Serum CK level was 467 U/L (normal range, 50–310). MRI revealed diffuse cerebellar atrophy (Figure ). EEG showed increased slow waves, paroxysmal sharp-slow wave in the frontal and temporal region (Figure ). The motor nerve conduction velocities were normal and compound muscle action potentials amplitude decreased (Table ). The sensory nerve conduction velocities and the sensory nerve action potentials were within the normal range (Table ). F waves with increased amplitudes were found in the left tibial nerve (Supplementary Material_Figure ).
Needle EMG revealed very little or no spontaneous activity (fibrillation, positive sharp wave, and fasciculation potentials) in all investigated muscles (musculus quadratus labii inferioris, sternocleidomastoid, paravertebral muscle, biceps, abductor digiti minimi, tibialis anterior muscle). Large amplitude, long duration motor unit potentials, as well as reduced recruitment were shown in the muscles mentioned above. In summary, this patient (III-1) showed an obvious motor neuron disorder phenotype as its initial and dominant symptom, which mimicked juvenile-onset amyotrophic lateral sclerosis (ALS), accompanying with relatively slight cerebellar ataxia, mental retardation (FIQ < 70), and ankle arthrogryposis (Table ).
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pmc-6306413-2
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The proband (II-2) was a 22 year old man from a non-consanguineous family with healthy parents and elder sister (Figure ). He firstly reported cognitive decline at the age 15, especially for the difficulty in study. At age 20, he developed a spastic-ataxic gait, followed by slurred speech. Neurological examinations revealed clinical signs of cerebellar ataxia, increased muscle tension in lower limbs, hyperreflexia in upper and lower limbs, positive pathologic reflexes, ankle clonus, with normal muscle strength, and volume (Table and Figure ). MRI of the brain showed diffuse cerebellar atrophy (Figure ). NCS demonstrated normal sensory nerve conduction and motor nerve conduction (Table ). Needle EMG revealed very little or no spontaneous activity (fibrillation, positive sharp wave, and fasciculation potentials) in multiple muscles (musculus quadratus labii inferioris, sternocleidomastoid, paravertebral muscle, biceps, abductor digiti minimi, tibialis anterior muscle). Large amplitude, long duration motor unit potentials, as well as reduced recruitment were shown in these muscles. In summary, this patient (II-2) shows as a mild ataxia phenotype, and subclinical motor neuron disorder, with cognitive decline.
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pmc-6306452-1
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The patient, female, 42 years old, was recruited in the study 16 months after hemorrhagic stroke. Following the MRI data the lesion was located in cortical-subcortical areas of the frontal lobe in the left hemisphere (Figure ). The muscle tone and tendon reflexes of the paretic arm were increased. The patient was able to follow the instructions of the rehabilitation procedure (the score of Montreal Cognitive Assessment amounted to 26) and had no other neurologic, neuromuscular or orthopedic diseases. The muscle force was assessed by Medical Research Council (MRC) scale as 1 for distal domain of the arm and as three for proximal one during all the three hospitalizations. Anxiety and depression were assessed by Hospital Anxiety and Depression Scale (HADS) () as 4/4 for first and second hospitalizations which corresponds to the norm (< 7) and as 8/7 for the third one, which corresponds to subclinical anxiety/depression. The patient went in for sports and was familiar with kinesthetic motor imagery. In addition, the patient was highly motivated for rehabilitation, which stimulates the efficiency of BCI-based procedures (, ). The patient met the inclusion criteria elaborated for the BCI+ Exoskeleton clinical trials ().
The patient went through three 2-weeks hospitalizations with 4 and 8 months intervals, respectively. She was provided with standard therapy in accordance with Russian treatment protocols and standards. Each hospitalization the therapy was complemented with 10 BCI+ Exoskeleton sessions, one session a day.
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pmc-6306562-1
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Case-1. A 48-years-old male patient who presented with intraventricular hemorrhage underwent combined STA-MCA bypass and EDAS surgery. Follow-up DSA showed direct bypass was almost occluded, yet revascularization was satisfying (Matsushima level 3) due to abundant dural neoangiogenesis. CTP demonstrated improved perfusion at temporal region. This patient had improved symptoms during follow-up. DSA and CTP images are shown in Figure .
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pmc-6306562-2
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Case-2. A 50-years-old female patient who presented with intraventricular hemorrhage underwent direct bypass surgery. Follow-up DSA showed patent bypass supplying around 2/3 of MCA territory, leaving a “blank” area in the temporal and parietal region. Dural neoangiogenesis was poor. This patient had a recurrent bleeding 17 months after the surgery. DSA images are shown in Figure .
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pmc-6306852-1
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An 87-year old woman from Junín, a rural area of the municipality of Venadillo, Tolima, Colombia, endemic for dengue, chikungunya and Zika [,], consulted at the local hospital. She complained of upper abdominal pain, arthralgia, myalgia, hyporexia, malaise and intermittent fever accompanied with progressive jaundice. She had a medical history of chronic heart failure (Stage C, New York Heart Association, NYHA III), without documented cardiac murmurs, right bundle branch block, non-valvular atrial fibrillation, hypertension, and chronic venous disease. On physical examination, she was conscious and had tachycardia, tachypnea, mucocutaneous jaundice, venous neck pulsations with abdominojugular reflux, increased S1 intensity with irregular rhythm, a systolic murmur at both upper sternal borders, and diminished breath sounds at both lung bases. Abdominal and neurological findings were unremarkable, with a non-painful palpable liver 3 cm down the costal border at the mid-clavicular line. Haematological evaluation showed leucopenia, and thrombocytopenia; other test results are shown in .
The electrocardiographic evaluation showed an atrial fibrillation with rapid ventricular response and right bundle branch block. The chest X ray showed cardiomegaly and bilateral pleural effusion. The patient was initially managed as severe dengue with hepatic compromise and she was transferred to an intensive care unit (ICU). After her admission in ICU she had one episode of hypoglycemia and her renal function gradually worsened. Alongside supportive treatment, antibiotic therapy with cephazolin was initiated. Her cardiac and pulmonary status quickly deteriorated after 24 h of admission without electrocardiographic changes, and she required ventilatory and vasopressor support. In the next hours, the patient evolved to pulseless electrical activity and died.
Blood samples were tested at the Public Health Laboratory of Tolima. Dengue IgM-antibodies (44.4% sensitivity, 99.1 specificity) and non-structural protein 1 (NS1) dengue protein through enzyme-linked immunosorbent assay (ELISA) (93.9% sensitivity, 97.4% specificity) were both positive []. Additionally, titers against Leptospira interrogans (serogroup Tarassovi, serovar Tarassovi, 1:400) were detected through non-paired microagglutination test (MAT) (93.8% sensitivity, 90.4% specificity) []. Chikungunya infection was confirmed with reverse transcription polymerase chain reaction (RT-PCR) (90% sensitivity, 100% specificity) []. Zika RT-PCR was negative (). Necropsy was not performed in the patient.
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pmc-6306916-1
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A 42-year-old Hispanic man with diabetes mellitus (DM) type 2 diagnosed five years ago and regularly treated with glybenclamide 5 mg once daily. Otherwise, the patient’s personal and familiar past medical history was unremarkable. He also denied consumption of alcohol, cigarettes, and illegal drugs. He presented to emergency department (ED) on 1 September 2017 with a history of malaise, headache, fever, and generalized body pain during the last 6 days. Three days before admission, he developed watery diarrhea (3 to 4 times a day), tachypnea, and confusion. During the following days, malaise and bowel movement frequency increased (up to 6 times a day). On the day of admission, the patient became drowsy, dyspneic, and looked very ill.
Physical examination: Body weight 50 kg, Body Mass Index 16.8 kg/m2, blood pressure: 60/30 mmHg, respiratory rate: 32 bpm, heart rate: 78 bpm, axillar temperature: 36 °C, SatO2: 99% (FiO2: 0.21); the patient was severely dehydrated, thyroid gland was not palpable; respiratory system: tachypnea, Kussmaul’s breathing; cardiovascular system: Sweaty mottled skin, and cold extremities with prolonged capillary refill time; neurologic system: Tremor in both hands, patellar and ankle hyperreflexia.
Lab: Hemoglobin 12.9 g/dL, hematocrit 40, platelets 198,000/mm3, white blood cells 10,100/mm3, segmented neutrophils 70%, bands 1%; serum glucose 460 mg/dL, urea 115 mg/dL, creatinine 1.3 mg/dL. Arterial blood gas analyses (ABG) are shown in . Liver function tests were normal, except for hypoalbuminemia and hypoproteinemia (3.0 g/dL and 5.18 g/dL, respectively). Urinalysis: pH 5, urine density 1030, leukocytes 2–4/field, granular casts 3+, glucose 3+, ketones 2+, and leucocyte esterase was negative.
Treatment with intravenous normal saline, potassium chloride, insulin infusion, sodium bicarbonate, norepinephrine, and empiric antibiotics (ceftriaxone + metronidazole) was administered. After 10 h of intensive treatment, ABG did not change significantly. So, differential diagnosis was extended and complementary exams were ordered: plasmatic amylase 96 U/L (reference range: 28–100 U/L), lipase 17 U/L (13–60 U/L), TSH 0.024 μIU/L (adult reference range: 0.27–4.2 μIU/L), free-T4 2.16 ng/dL (reference range: 0.82–1.63 ng/dL), total-T3 0.18 ng/mL (reference range: 0.5–2.0 ng/mL), free-T3 0.42 pg/mL (reference range: 2.1–3.8 pg/mL); CPK-MB 101.3 U/L (reference range: 0–25 U/L), total CPK 505.7 U/L (normal: 39–308 U/L); troponin T 25.0 ng/mL (reference range: 0.12–0.6 ng/mL). Based on these results, hydrocortisone 100 mg every 8 h, methimazole 20 mg every 8 h, and Lugol’s solution 10 drops every 8 h, were added on the second day of treatment. Because of shock, beta-blocker was not administered. On the third day of treatment a good evolution was observed, norepinephrine and insulin infusion were discontinued, and NPH insulin was initiated. Based on physical examination, chest x-ray (CXR) ( and ), and progressive decrease in partial oxygen pressure () compatible with acute lung edema, intravenous furosemide 20 mg every 12 h was administered for 2 days.
Although ECG was normal, troponin determinations were repeated over the next days and persisted elevated. Echocardiography (5 September 2017) showed borderline pulmonary artery systolic pressure (35 mm Hg), severe LV systolic dysfunction (LV ejection fraction 35%), diastolic dysfunction of restrictive type and global hypokinesia ().
On the 6th day of treatment, hydrocortisone and Lugol’s solution were stopped, and methimazole was reduced by half. The patient was discharged on 7 September 2017, with almost complete recovery.
We also performed other complementary exams: Twenty-four hour-urine sodium, chloride, and potassium levels were also normal. Direct stool examination showed 0–1 leucocytes/HPF, no parasites, no blood, no erythrocytes. Urine culture and HIV serology was negative. Anti-TPO and anti-thyroglobulin antibodies were negative. Cardiac catheterization and endomyocardial biopsy were not performed. Follow-up echocardiography at 6 months was completely normal. After the patient was discharged, no additional (blood or imaging) study was performed, other than echocardiography.
Written informed consent was obtained from the patients for publication of this article and accompanying images.
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pmc-6306986-1
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An 8-year old male was admitted at the Red Cross Children's Hospital, Cape Town, through the Trauma Emergency Department. The patient was brought to the Trauma Resuscitation room in the hospital's casualty by family members with a history of pedestrian vehicle accident. He was unconscious at the scene of the accident but there was no seizures or vomiting. In the resuscitation room, he was found to be breathing spontaneously with an oxygen saturation of 100%. He had a blood pressure of 110/82 mmHg and a pulse rate of 97 beats/min. His Glasgow coma scale (GCS) was 12/15 (E3M5V4) but improved to 15/15 by the following day. He had equal and reactive pupils bilaterally. There were abrasions on the forehead and oozing of blood from the nostrils, and tenderness at the upper part of the back of the neck in the midline, but there was no neurological fallout. A low dose whole body x-ray (LODOX) performed in the trauma resuscitation room revealed an abnormal C2 vertebral body with evidence of subluxation and atlantodens interval (ADI) of 4.9mm ( and ).
A CT scan of the brain performed on the same day revealed an essentially normal brain and an old fracture of C2 traversing through the transverse foramina of C2. There was associated posterior subluxation of C2 on C3 with narrowing of the spinal canal at C2/C3 level, but there was no associated prevertebral soft tissue swelling ( and ).
He was subsequently placed on C-spine precautions and soft cervical collar but while on admission in the ward the following day, this was changed to an Extension Halter traction. A follow up plain C-spine X-ray (mobile) performed same day the Halter traction was commenced and with comparison made to the previous LODOX study, revealed significant subluxation of C2 on C3 with fractures of bilateral pars interarticularis ().
However, there was no significant interval change with the LODOX study. The atlantodens interval (ADI) was 3mm and there was no significant prevertebral soft tissue swelling as well. The Halter traction was discontinued and soft cervical collar re-instituted and the head supported by head blocks. On account of persistent exquisitely tender midline upper C-spine, an MRI of the C-spine was performed on the 3rd day post admission and in comparison with the CT study. The MRI identified the fracture/subluxation of C2, and revealed an intact but displaced intervertebral disc between C2 and C3 protruding into the intraspinal canal and causing cord compression. There was associated abnormal high signal intensity extending from C1-C2/C3 intervertebral disc space. Of concern was that the prevertebral soft tissue swelling increased from the CT study and measured 16mm (previously 8mm) and as well showed fluid content ( and ).
Given the change in prevertebral soft tissue swelling, the radiologist considered the MRI features to be consistent with acute on chronic C-spine injury with associated cord signal changes. On the 2nd night post admission/injury and after discontinuation of the traction, the patient was noticed to be bradycardic with his pulse rate falling as low as of 40 beats/min, but with stable blood pressure.
He was subsequently admitted in the Paediatric Intensive Care Unit (PICU) to monitor for autonomic dysfunction. A review on the 3rd day post admission by the Spinal Unit revealed decreasing motor power in the upper limbs (4/5 in all muscle groups) and lower limbs (3/5), intact sensations and evidence of upper motor neuron signs. The case was subsequently presented on day 7 post admission at the Spinal Meeting, comprising spine surgeons from the Spinal Unit, Department of Orthopaedic Surgery and Department of Neurosurgery, Groote Schuur Hospital as well as other practicing Spine Surgeons in Cape Town. After extensive deliberations on the pros and cons of conservative versus surgical intervention for this particular traumatic lesion, decision was taken to intervene surgically. On day 10 post admission, a C2-C3 anterior cervical discectomy and fusion (ACDF) using a 4-hole titanum plate/screws and autologous iliac crest bone graft was performed (, and ).
The intraoperative findings revealed an intact C2-C3 intervertebral disc which was, however, found to be separated from the C3 superior endplate through the cartilaginous layer. This probably was the factor in the unusual radiological appearance of the subluxation which showed the anteroinferior edge of C2 vertebra sitting on the superior surface of C3 vertebra with associated posterior displacement of the C2 vertebral body and its attached C2-C3 intervertebral disc into the spinal canal. Also there was clear evidence of acute injury and no signs of an old injury as evidenced by the absence of facet ankyloses and the relatively easy reduction. The soft cervical collar was continued post-operatively. The patient remained stable, recovered full motor power and was actively mobile post-surgery. He was subsequently discharged home on day 7 post surgery to the care of his Aunt and for outpatient follow up in the Paediatric Spinal Clinic as well as with Social Workers. It is of note that despite the radiological consideration of the C2 fracture as an old fracture, there was no history of any previous cervical spine trauma. However, a lot of social issues were uncovered during the patient's hospitalization necessitating the involvement of the hospital Social Workers in the care of the patient. The patient was discharged to the care of his Aunt, with no objection from the mother of the patient. A follow up plain cervical spine X-ray showed adequate reduction and satisfactory alignment of C2-C3 with the anterior cervical plate/screws in-situ ().
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pmc-6307108-1
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A 24-year-old South African-Indian man, a medical student, had presented 6 years earlier to his peripheral hospital with complaints of lethargy and weakness, chronic constipation and lower backache, and episodes of hematochezia, associated with anorectal pain. These symptoms started 18 months earlier. The clinical examination was unremarkable. Routine blood tests were otherwise normal except for marked polycythemia (Table ). A colonoscopy was performed, and a biopsy taken from a sessile rectal polyp; however, no specific pathological diagnosis could be made, and he was referred to our center for further management.
At our gastroenterology clinic, the initial presentation together with a review of the rectal biopsy were considered suggestive of ulcerative colitis and he was initiated on 5-aminosalicylic acid and, later, sulfasalazine. However, the symptoms did not improve, and these drugs were stopped. During this time, it was noticed that his blood pressure was 156/86 mmHg, and treatment with enalapril was initiated. After a period of approximately 4 months, the enalapril was stopped because he had no evidence of left ventricular hypertrophy on an electrocardiogram or echocardiography and 24-hour ambulatory blood pressure monitoring was normal. A repeat colonoscopy was performed, this time revealing rectal prolapse. The gastrointestinal symptoms resolved completely without the need for further medication.
During this period, he was also investigated for the polycythemia at our hematology clinic. A blood test for the Janus kinase-2 (V617F) mutation was negative and the blood erythropoietin concentration was normal (Table ), hence, excluding primary polycythemia. Due to the severity of the polycythemia, he received frequent venesections that resulted in lethargy, and the venesections were subsequently stopped. Other investigations for true polycythemia were normal and included: a venous blood gas to determine the P50 value for hemoglobin oxygen affinity; echocardiography to rule out congenital cyanotic heart disease; polysomnography for obstructive sleep apnea syndrome; and an abdominal ultrasound for hepatocellular carcinoma, polycystic kidney disease, renal cell carcinoma, and renal arterial stenosis. A radioisotope study showed that the red cell mass was within the normal range; however, the plasma volume was reduced, suggesting relative polycythemia. After approximately 5 years, he was referred to the nephrology unit for further investigation.
At this time, there were no symptoms of nausea, vomiting, diarrhea, polyuria, or nocturia. Once again, he confirmed that he never felt thirsty, even during the previous episodes of hypernatremia. He drank water out of habit rather than in response to thirst. He was not using any prescription drugs, including diuretics. His family history included a father with diabetes mellitus and hypercholesterolemia and a mother with hypertension. He did not smoke tobacco or consume alcohol. He led a relatively sedentary lifestyle and did not participate in any outdoor recreational activities. He was in his final year of medical school training. A clinical examination was unremarkable. He was euvolemic and there was no evidence of postural hypotension. No cognitive or focal neurological deficits were identified. A urine dipstick was normal. His weight was 96 kg and height 1.70 m (calculated body mass index of 33.2 kg/m2). Bioimpedance spectroscopy (Body Composition Monitor ®, Fresenius Medical Care, Germany) was used to further assess his hydration status and revealed a total body water volume which was 800 mL less than predicted.
A blood sample for serum sodium concentration was drawn and revealed a value of 151 mmol/L (reference range 138–145 mmol/L; see Table ). Previous urine osmolality samples showed excellent urinary concentrating ability, thereby excluding a diagnosis of diabetes insipidus. A diagnosis of hypodipsia was made, and he was asked to drink 2 liters of water daily for 1 week. Blood and urine samples were then repeated and revealed normalization of the serum sodium concentration while maintaining urinary concentrating ability, thus confirming our suspicion of hypodipsia (Table ). Since hypodipsia has been reported to be the result of a hypothalamic lesion, magnetic resonance imaging of his brain was performed but no intracranial pathology was identified (Fig. ). He was instructed to continue drinking at least 2 liters of water daily. On follow-up 6 weeks later, he remained clinically well and did not report any significant change in his symptoms.
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pmc-6307113-1
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A 56-year-old female patient was transferred to our department of critical care medicine, Huashan hospital in Shanghai in June 2016 after she received treatment in a local hospital for productive cough, tachypnea and respiratory distress. She complained of recurrent fever and asymmetric edema of the lower extremities for over 1 month, as well as painful swelling both in the thyroid and labium majus for 2 weeks. In the previous hospital, due to the finding of multiple bilateral cysts which were palpable nodules in her thyroid gland by ultrasound examination, a left lobe thyroid puncture and drainage had been conducted and an aspergillus fumigatus infection was detected. She had a history of systemic lupus erythematosus (SLE) and lupus nephritis for 8 years, and received prednisone treatment for these diseases. But from November 2015, prednisone was switched to methylprednisolone, and hydroxychloroquine has been added because of lupus nephritis aggravation, and tacrolimus has also been added to the medications in the following month. She was also diagnosed with renal hypertension and diabetes induced by steroids, and received antihypertension and antihyperglycemic therapy. She had no history of pulmonary diseases such as chronic obstructive pulmonary disease (COPD), asthma, or any repeated infections, and had no addiction to drugs, smoking or alcoholism. Previous examinations showed no evidence of neutropenia. The ratio of CD4/CD8 was 0.33. Only one aspergillus test was positive in repeated sputum cultures. The galactomannan aspergillus antigen and culture tests in BALF were negative, so were blood and urine cultures including fungi. Our chest computed tomography (CT) imaging revealed bilateral patchy lung opacities in the middle and lower lobes, along with multiple shadows of fibrotic streaks, high-density nodules and mediastinal calcification of lymph nodes (Fig. ). The diagnosis of pulmonary infection was established, and pathogen was highly suspected of aspergillus according to the previous finding of thyroid puncture and drainage. An ultrasound examination showed thrombosis in the bilateral femoral veins and popliteal veins. In addition, a 51 × 16 mm hypoechoic lesion was detected in the left subcutaneous perineal region. We continued voriconazole therapy in a standard treatment dose (200 mg twice a day), but her body temperature was still up to 37.6 °C intermittently. Her white blood cells were 15.61 × 109/L (neutrophils 90.8% and lymphocytes 5.4%), hemoglobin was 93 g/L, and platelets were 295 × 109/L. Except hyperglycemia, proteinuria, and hypoproteinemia, other routine laboratory tests were unremarkable, which including thyroid hormone levels. A neck CT showed findings consistent with a fluid collection in the right thyroid lobe (Fig. ). Cultures of aspirated purulent fluid showed aspergillus fumigatus growth, which was obtained from fine needle aspirations in both thyroid and perineum. Five days after being transferred to our hospital, the patient’s thyroid drainage tube was removed because no further fluid was drained out. We continued the voriconazole dose 400 mg per day as anti-aspergillosis therapy with 16 mg methylprednisolone and 400 mg hydroxychloroquine per day as immunosuppressive therapy, along with a therapeutic 4100 iu q 12 h dose of nadroparin calcium. The patient’s fever was relatively controlled and white blood cells decreased to 10.74 × 109/L (neutrophils 91.7%, and lymphocytes 4.7%). Lesions in the thyroid and subcutaneous labium majus became significantly smaller, and the pain was greatly relieved. On the eighth day of hospitalization, the symptoms had improved and the patient was discharged from our hospital. She continuously took voriconazole orally (400 mg per day) for 6 months, combined with caspofungin for the initial 2 weeks (first day 70 mg, then 50 mg per day). After 1 month of antifungal treatment, she was afebrile and all the clinical symptoms were relieved. The patient is on a follow-up for 1 year and has been free of aspergillosis for 6 months. Hydroxychloroquine treatment ceased in April 2017, and methylprednisolone dose was reduced in a tapered manner.
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pmc-6307122-1
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A 68-year-old man presented a weight increase of 7 kg during the last year and symptoms compatible with hypoglycemia (objective vertigo, feeling of an empty head, sweating, palpitations). During some of these episodes low blood glucose levels (< 40 mg/dl) were documented by glucometer measurement. The symptoms regressed with food intake. These episodes initially occurred during physical activity and later also during fasting.
He had no family history of endocrine disease.
At admission, his body mass index was 28 kg/m2. The rest of the physical examination was unremarkable. Biochemical assessment did not show any abnormality, and glucose level was 70 mg/dl (n.v. 65–110). Plasma cortisol at 8 a.m. was in the normal range (394.8 nmol/l, n.v. 138–685 nmol/l), anti-insulin antibodies were negative, chromogranin A was 69 ng/ml (n.v. 10–185), prolactin was 247 mU/l (n.v. 53–369), gastrin was 12.7 pg/ml (n.v. < 180), PTH was 6.4 pmol/l (n.v. 1–6.8) and serum calcium level was 8.8 mg/dl (n.v. 8.6–10.4).
The fasting test was performed, which was interrupted after 12 h due to the onset of symptomatic hypoglycemia (44 mg/dl, glucometer measurement). Plasma glucose level was 41 mg/dl, insulin level 16.3 U/L and C-peptide 1.27 nmol/l (Table ). Per protocol, 1 mg of glucagon was injected intravenously after interruption of the fasting test and plasma glucose was measured (time 0′, 41 mg/dl; after 10 min 75 mg/dl, after 20 min 94 mg/dl and after 30 min 93 mg/dl). The patient’s laboratory results showed endogenous hyperinsulinemia, according to published guidelines (fasting test: plasma glucose < 55 mg/dl, with insulin and C-peptide levels > 3 U/L and > 0.2 nmol/L, respectively; glucagone test: > 25 mg/dL increase of glucose levels after fasting) []. The short octreotide test (subcutaneous infusion of 100 mg of short-term octreotide at 7.00 a.m. after an overnight fast, and blood glucose, insulin and C-peptide hourly sampling for six hours) was performed to evaluate the efficacy of a possible treatment with somatostatin analogs, in order to counteract hypoglycemia []. No food was allowed during the test. The test showed an increase in plasma glucose above 100 mg/dl (Table ), and the patient was considered to be responsive to somatostatin analogs [].
Additional procedures included:MRI, which revealed a lesion of the uncinate pancreatic process of about 4 cm, which presented a brief contact with the upper mesenteric artery and a > 180° contact with the superior mesenteric vein with suspected infiltration (Fig. ). Octreoscan, which showed a lesion located in the pancreatic site, with a high somatostatin receptor (sstR) density (Fig. ). Abdominal CT scan with contrast, which revealed a polylobed lesion with sharp margins at the level of the uncinate pancreas process, in contact with the superior mesenteric vein and reaching the margins of the superior mesenteric artery. No signs of vessels infiltration were observed.
All these imaging procedures were indicative of the presence of an insulinoma as the cause of endogenous hyperinsulinemia.
Surgical treatment was scheduled. Before surgery, considering the response to the short octreotide test, the patient was treated with short acting octreotide (0.1 mcg twice a day), obtaining a good control of glycemia by glucometer measurement, disappearance of hypoglycemic symptoms and no recurrence of hypoglycemic episodes.
The patient underwent exploratory laparotomy and duodenocephalopancreasectomy after one month.
The postoperative course was complicated by the appearance of a pancreatic (grade B) [] and a biliary fistula, whereby the patient was conservatively treated with fasting and parenteral nutritional intake and subsequenty via a naso-enteral tube. The control CT scan, performed a month later, did not reveal intra-abdominal spill and drainages were removed. Oral feeding was resumed one month after the operation.
The definitive histological examination revealed a neuroendocrine tumor with insulin receptors (insulinoma) of 3.5 cm infiltrating the duodenum, retroperitoneal adipose tissue, with widespread neoplastic thrombosis, and with metastasis in 3 pancreatic-duodenal lymph nodes among the 48 that had been surgically removed (T3N1MO, AjCC VIII edition G1), with a low replicative index (Ki67: 2%); radical resection (R0). Vascular and adipose tissue infiltration by the tumor, which are indicative of malignancy, were observed. Immunohistochemical staining was positive for insulin and synaptophysin (Fig. ).
The most recent abdominal MRI, performed 6 months after surgery, did not reveal any recurrence of disease and currently the patient is in good conditions and with normal glycemic levels.
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pmc-6307137-1
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A 62 year-old male had displayed bradykinesia and tremor of his right limbs for one year, during which he was able to perform limited fine movements such as dressing himself, lacing up his shoes and brushing his teeth. His tremors were aggravated by nervousness and relieved when asleep. He had had a history of hypertension and took a daily dose of 5 mg amlodipine. The patient had no history of any other chronic illnesses and was not on any other type of medication. Neither the electrocardiogram nor the Holter monitor showed any abnormalities. His baseline recumbent-upright blood pressure (BP) and heart rate (HR) were normal prior to treatment with piribedil, as shown in Table . He was diagnosed with PD based on the Movement Disorder Society clinical diagnostic criteria []. Initially, he received dopamine replacement therapy of 50 mg piribedil per day. Although there was no significant improvement in symptoms neither did he feel any discomfort. Therefore, starting the first dose change of piribedil, he added extra 50 mg to his dose. About two hours later after the first change in dose, the patient experienced symptoms of dizziness and sweating; he collapsed half an hour later. Whilst in a sitting position, the patient’s BP and HR were measured immediately. The BP reading was 85/48 mmHg and HR was 45 beats/min. His symptoms continued for the duration of the day with sitting BP fluctuating between 80–95 mmHg to 45–68 mmHg. Because his head computerized tomography examination found no abnormalities, the patient received 500 mL of 0.9% sodium chloride solution, after which his symptoms improved. Due to adverse drug reactions (ADRs), the patient was started on a second dose change of piribedil, i.e. an extra dose of 25 mg piribedil was to be taken in the afternoon in addition to the existing 50 mg taken in the morning. After two and a half hours, the patient experienced dizziness, sweating, nausea and vomiting, with a BP reading of 70/45 mmHg and a HR of 47 beats/min when sitting. His BP recovered to 105/65 mmHg and HR to 60 beats/min after elevating his lower limbs and resting for 20 mins. As a result of these incidences, the patient was switched to pramipexole to replace piribedil. After taking pramipexole 0.125 mg or 0.25 mg three times a day (tid), the symptoms of hypotension and bradycardia disappeared but a reduced amplitude of his right arm swing was still observed. Finally, after the pramipexole dose was increased to 0.375 mg tid, the patient showed marked improvements in motor symptoms. The changes in BP and HR are shown in Fig. .
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pmc-6307139-1
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A 6-year-old female with Down syndrome presented at our emergency department with a 24-h history of fever, left hip joint pain and limping. She had been previously diagnosed with compensated mitral valve prolapse, reported a past episode of pneumonia and underwent adenotonsillectomy for obstructive apnea 3 years earlier. One month before admission she traveled to Cuba with her family. On admission, she was febrile with left coxofemoral joint pain and movement impairment. Blood tests showed increased white cells count (WCC) with neutrophilia (WCC 23070/mm3, N 90%) and a raised C reactive protein (CRP 10 mg/dl, normal < 0.29 mg/dl). A left coxofemoral ultrasound documented a 10 mm intra-articular fluid effusion.
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pmc-6307139-2
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A 9-year-old male attended the emergency department with a 3-days history of right ankle joint pain non-responding to non-steroidal anti-inflammatory drugs, limited joint movement and apyrexial. The child had been adopted from Hungary the year before and was diagnosed and treated for Toxocariasis at the baseline health screening as an adopted child. There was no recent history of close contact with other children and no history of respiratory or urinary tract infections.
Blood tests showed increased WCC with neutrophilia (WCC 13700/mm3, 70% N), C reactive protein (CRP 11 mg/dl, normal < 0.29 mg/dl), and erythrocyte sedimentation rate (ESR 64 mm/h, normal < 15 mm/h). A right hip X-ray was normal, whereas right hip ultrasound showed an 11-mm intra-articular effusion and swelling of the right synovial capsule. He did not present any other location of arthritis or arthralgia.
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pmc-6307157-1
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A 70-year old male patient reported to clinic with a chief complaint of swollen gums of 5 year duration and wanted to replace his missing teeth. Patient noticed swollen gums prior to his 4 years of edentulous state and the condition persisted to present. He was a known hypertensive and was on medication for the same since 7 years (10 mg Nifedipine/day).On intraoral examination- pink, firm, irregular, nodular, non- tender enlargements were found on labial aspects of maxillary and mandibular residual alveolar ridges. The enlargements were asymptomatic in nature with no history of bleeding. Both arches were completely edentulous (Fig. ). Panoramic radiograph showed no osseous deformities of maxilla and mandibular ridges (Fig. ). Patient’s complete blood count, bleeding time, clotting time and platelet count were with in normal limits. An incisional biopsy was obtained from anterior right side of the maxilla. Histological report revealed hyperplastic and acantholytic stratified squamous epithelium with elongated rete ridges extending into connective tissue which was fibro collagenous and showed focal areas of fibrosis. Infiltration of chronic inflammatory cells and congested blood vessels were seen which suggested of gingival hyperplasia (Fig. ). As patient wanted complete dentures, we planned to surgically excise entire overgrowth. Considering medical status of the patient, drug was not altered because, dose taken by the patient was low (10 mg/day). Local anesthesia devoid of vasoconstrictor was used to remove fibrous tissue from alveolar ridge with help of 15 no. B.P blade (Fig. ). To avoid any discomfort during the early phase of wound healing, a surgical splint was placed on both ridges after thoroughly covering the operated site with periodontal dressing (Coe Pack). The patient was recalled and followed at a period of 1 week, 3 months, 6 months and 1 Year intervals (Figs. , , and ). No recurrence of growth was observed during any of the recall visits. After 3 months of surgery, patient had his complete dentures fabricated. Even on further recall visits there was no recurrence of growth noticed.
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pmc-6307169-1
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A 67-year-old male patient diagnosed with stage IV pulmonary adenocarcinoma was first treated with 6 cycles of carboplatin and pemetrexed followed by a maintenance regimen. Progression occurred within fourteen month after the start of the initial treatment. Consequently, second-line nivolumab was initiated at a dose of 3 mg/kg every two weeks.
After thirteen doses of nivolumab, the patient complained of irritated red eyes without visual impairment. He did not exhibit skin involvement, arthralgia or urinary tract or digestive symptoms. The conjunctiva swab test was negative, and no improvement was observed with antibiotic ocular drops. The ophthalmologist’s examination revealed bilateral sterile conjunctivitis with no signs of uveitis or retinal lesions (Fig. a). The patient was treated with topical steroids with partial improvement.
A few days later, he developed fatigue and progressive dysphagia which became severe after two months followed by rapid 10-kg weight loss without symptoms of associated colitis or gastritis. At that point, the main differential diagnosis was esophageal infection, tumor progression with gastrointestinal (GI) upper tract involvement, paraneoplastic syndrome [] or an atypical checkpoint inhibitor-related adverse event. Of note, the patient had no history of personal or familial autoimmune disease, conjunctivitis or upper digestive tract abnormality prior to nivolumab treatment. The oral examination initially revealed evidence for oral candidiasis, but treatment with a 7-day course of fluconazole did not improve dysphagia despite the resolution of the stomatitis. Bacterial culture of the oropharyngeal swab was negative, and PCR results for herpes simplex 1 and 2 infection were also negative. A blood sample revealed a discrete increase in the erythrocyte sedimentation rate (ESR) with no eosinophilia or leukocytosis. Liver and kidney function panel tests were normal. Thoracoabdominal CT scan reported no evidence of disease recurrence. Due to patient fatigue, a therapeutic break was implemented for one month with the introduction of prednisone at 30 mg per day with rapid tapering over 1 month. Although the patient initially experienced a partial resolution of dysphagia, a quick recurrence of symptoms was noticed as the prednisone dose was tapered. One month later, nivolumab was restarted, and the patient noticed a rapid deterioration of his dysphagia and mucositis. The clinical situation deteriorated despite the introduction of nystatin and steroid mouthwash, and the patient continued to lose weight. An esophagogastroduodenoscopy was done, which revealed diffuse mucositis with a scar-like stenosis immediately below the upper esophageal sphincter (Fig. b). Unlike the upper esophagus, the lower part and the stomach were of normal appearance.
Biopsies of the oropharynx were performed, but esophageal dilatation was not performed due to the highly inflammatory mucosal status and patient anticoagulation. Faced with this significant loss of weight and the impossibility of an oral diet, a nasogastric tube was placed. Biopsies of the oropharynx displayed marked lymphocytic inflammation and several foci of monocellular necrosis in the squamous epithelium. Morphologic evidence of adenocarcinoma and signs of mycotic, bacterial or viral infection were not observed. Immunohistochemical stainings were performed in an automated stainer (Benchmark XT; Ventana Medical Systems, Tucson, AZ) using 3 μm-thick sections and the following antibodies: CD45 (monoclonal, clone 2B11 + PD7/26, Dako, Glostrup, Denmark), CD19 (monoclonal, clone BT51E, Novocastra, New Castle, UK), CD20 (monoclonal, clone L26, Novocastra), CD3 (monoclonal, 2GV6, Ventana), CD4 (monoclonal, SP35, Ventana), CD8 (monoclonal, C8/144B, Dako), CD68 (monoclonal, clone KP1, Dako), and PD-1 (polyclonal, R&D System, Inc., Minneapolis, MN, USA). Immunohistochemistry revealed a florid immune infiltrate, predominantly with T cells (90% CD45+CD19−CD20−CD3+), with only 10% of B cells (CD45+CD19+CD20+CD3−). Among T cells, the majority (80%) were CD4+. Few T cells expressed PD-1+. Rare macrophages were also observed (Fig. ).
Based on these results, esophageal stenosis was considered a severe irAE secondary to an important mucosal inflammatory infiltrate. This severe dysphagia required enteral feeding, and nivolumab was permanently discontinued after seventeen doses. The patient was treated with 125 mg methylprednisolone followed by 1 mg/kg oral prednisone (total dose: 80 mg). After 3 days of treatment, the patient reported significant improvement, enabling him to eat solid food. Prednisone was tapered by 20 mg every two weeks until reaching a daily dose of 40 mg after 45 days of prednisone tapering, when he again presented increasing symptoms of severe dysphagia.
The patient was treated a second time with 125 mg methylprednisolone for 3 days followed by 1 mg/kg oral prednisone (total dose: 80 mg) with amelioration of dysphagia. Three weeks later, after the reduction of prednisone to 60 mg/daily, the patient noticed a new severe dysphagia deterioration, remaining aphagic. In this context, quick endoscopic esophageal dilatation was attempted. The laryngeal margin and hypopharyngeal mucosa appeared highly inflamed with fibrinous deposits on the direct laryngoscopy with no sign of salivary stasis or tumor invasion. Rigid esophagoscopy revealed erythema of the oropharynx with friable nonulcerative mucosa and an inflammatory aspect of the entire esophagus. Concomitant high-dose steroids at a dose of 125 mg of methylprednisolone for 3 days followed by 1 mg/kg prednisone again allowed transient symptomatic improvement.
One month later, recurrent dysphagia did not permit steroid tapering under 50 mg/d. Furthermore, the long course of high-dose corticosteroid treatment was complicated with severe osteoporosis and several spontaneous compression fractures of thoracolumbar vertebrae. Pathologic fracture due to metastases was ruled out by bone biopsy.An enlarged T10 to L5 vertebral cementoplasty was carried out. One month later due to a new episode of recurrent major dysphagia, the patient received a new bolus of 125 mg of methylprednisolone for 3 days followed by 1 mg/kg prednisone. The serum level of IL-6 was 3.10 pg/ml (normal range < 1.5 pg/ml), measured the same day before tocilizumab administration. Serum levels of IL-6 were assessed by electrochemiluminescence (ECL) Elecsys® IL-6 (Roche; Switzerland) according to the manufacturer instructions.
At this point, a second line of immunosuppressive treatment was considered. Based on the oropharynx biopsy, histological analysis and the presence of a predominantly T-cell infiltrate, a single intravenous administration of the interleukin 6 receptor (IL-6R) neutralizing antibody tocilizumab at a dose of 8 mg/kg was given. This led to rapid amelioration of the symptomatology, with successful prednisone tapering without recurrent dysphagia. At the present time, 3 months after the administration of tocilizumab, the patient has experienced no relapse of dysphagia. A recent rigid endoscopy confirmed complete resolution of orolaryngopharyngeal and upper esophageal inflammation (Fig. ).
During immunosuppressive therapy we observed no tumor progression. Eight months after discontinuing nivolumab treatment, the patient remains in complete remission with no radiographic evidence of tumor relapse.
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pmc-6307190-1
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A 32 year old female Cameroonian gravida 4 para 3 at 34 weeks of gestation presented to the labour and delivery unit of Mbalmayo district hospital with 8 h history of severe generalized headache, expressive aphasia and right sided paralysis in an afebrile context. This was associated with blurred vision but no convulsions. There was no epigastric pain and no difficulty breathing and no history of trauma or fall. For this current pregnancy, antenatal care (ANC) was started at 18 weeks with a booking blood pressure of 100/70 mmHg. She did four ANCs and all were uneventful. During her routine four ANCs here blood pressure was always less than 140/90 mmHg and her urine dipsticks done during the four ANCs were all negative for proteinuria. She refused neurological symptoms such as headache during pregnancy. She has a history of gestational hypertension in her third pregnancy. There was no family history of chronic hypertension, diabetes and chronic kidney diseases. On examination she was afebrile with a blood pressure of 182/126 mmHg and pulse of 112beats/minute. Neurological examination revealed Glasgow coma score of 13/15, right sided hemiparesis and expressive Broca’s aphasia, no signs of meningeal irritation. The abdomen was distended by a gravid uterus with a fundal height of 35 cm, foetus in a longitudinal lie and cephalic presentation. The cervix was long, posterior, soft and closed with a station of − 1. We had a working diagnosis of severe pre-eclampsia complicated by stroke. Shown on Table are laboratory investigations done and their results.
An emergency obstetric ultrasound showed a life foetus with an estimated foetal weight of 2300 g at 33 weeks of gestation. Emergency cerebral non contrast-CT scan showed a 3.2 cm hyperdense region in the left parietal lobe with surrounding hypodensity due to clot retraction as shown on Fig. . Emergency management by the obstetrician consisted of MgSO4 using the Pritchard protocol [], which consisted of 14 g loading dose then 5 g maintenance every 6 h until 24 h after caeserean section; bethamethasone 12 mg intramuscular and reduction of blood pressure with nicardipine 5 mg/h. Four hours later an emergency caesarean section was done by the obstetrician under spinal anaesthesia and it let to the extraction of a life female with APGAR 8 and 10 at the 1st and 5th minute respectively and weight 2200 g. The management after caesarean section consisted of hospitalization in the intensive care unit with nicardipine titrated in an electric syringe at 2.5 mg/hour, ceftriaxone 2 g intravenous, Paractamol 1 g 8 hourly, and ringers lactate 6 hourly for 24 h. Post-operative management was done by a multidisciplinary team including a neurologist, cardiologist, intensive care physician, obstetrician, neonatologist and physiotherapist. On postoperative day 2 she was transferred from the intensive care unit to the maternity where she spends five additional days on nicardipine slow release 50 mg 12 hourly and paracetamol 1 g 8hourly and was later release after the ten days on nicardipine 50 mg daily and daily physiotherapy. Six weeks during routine postpartum visit the blood pressure was normal and patient was no longer aphasic and shet has regained the muscle strength partially. The baby was hospitalised in the neonatal unit for 10 days and discharged alongside the mother.
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pmc-6307234-1
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On December 2017, a 35-year old male was admitted into a peripheral hospital in northern Sicily, the patient had been suffering from a fever with chills (peaking to 39 °C) and back pain in the lumbar and dorsal area, for as long as 7 days.
He had an unremarkable clinical history, except for minor surgery because of anal fissure in November 2017.
After admission, the patient started, unsuccessfully, oral levofloxacin 500 mg/day and ceftriaxone 1 g/day intramuscularly.
A MRI of the vertebral column was performed showing vertebral lesions affecting multiple vertebral bodies (from D8 to L5). The major lesions were target-like and showed a peripheral hypointense circle in T2 sequence.
Due to the finding of leukopenia with lymphopenia, HIV serology was performed resulting positive. Viral Load (VL) was 4,370,000 copies/ml and T CD4+ count was 5 cells/μL. Antiretroviral therapy with emtricitabine/tenofovir disoproxil, ritonavir and darunavir was started.
On January 11th, with the hypothesis of bacterial spondylitis, the patient started an empirical antibiotic therapy with rifampicin and teicoplanin.
On January 17th, due to the persistence of fever and back pain, the patient was transferred to the Infectious Diseases Unit of Garibaldi Hospital in Catania (eastern Sicily).
On admission the patient was febrile (T. max 38,3 °C) with intense pain in the dorsal and lumbar area; blood pressure was 95/40 mmHg, heart rate was 124 bpm. Oxygen saturation was 97% in room air. Neurocognitive function was preserved as assessed by Mini Mental State Examination (MMSE) and International HIV-Dementia Scale (IHDS).
He vigorously and repeatedly denied any risk factor for exposure to HIV infection. He had no previous history of drug abuse, he denied having any type of sexual relationships with both females and males and he had never used blood products. He had not tattoos or piercings. He denied smoking or drinking alcohol. He was allergic only to strawberries.
Moreover, he had never had major surgery and he had never undergone any medical invasive procedures. He had no comorbidities so he was not taking any drugs or medication.
His medical family history was unremarkable.
Laboratory examinations showed normocytic anemia (Hb: 6,7 g/dl, RBC: 2,45 * 106/mm3), leukopenia with neutropenia (WBC: 1700/mm3), low platelet count (106,000/mm3); high values of CRP, ESR and ferritin levels.
Hepatitis B and Hepatitis C virus serology was negative, as well as TPHA and VDRL. Serum 1–3 Beta D glucan was < 60 pg/mL and Galactomannan was 0.08 Optical Density Index.
ART was immediately switched to emtricitabine/tenofovir alefanamide plus dolutegravir, in order to reduce pharmacological impact on bones and to preserve kidney function.
On January 19th, the patient performed a total body CT scan which showed multiple bilateral lung nodular lesions with paratracheal and mediastinal lymphadenomegaly (around 1 cm diameter); presence of multiple hypodense lesions involving spleen and liver (diameter between 1.5 and 2 cm). Mesenteric, iliac and lombo-aortic lymphadenomegaly was also present with a diameter of > 1 cm.
On January 20th, eight out of eight blood cultures gave a positive result for Cryptococcus neoformans; thus, induction therapy with liposomal amphotericin 3 mg/kg/die plus fluconazole 800 mg intravenously was started on January 21st obtaining a prompt remission of fever and rapid disappearance of lung nodular lesions. The induction therapy was administered for as long as 15 days. A lumbar puncture was performed but none of the cultures, antigenic tests nor the India Ink stain on CSF resulted negative for Cryptococcus. After the induction therapy, a series of repeated blood cultures resulted negative for Cryptococcus so maintenance therapy was started with fluconazole 400 mg.
On January 30th, due to a recurrence of fever and chills, additional blood cultures were performed resulting positive for Staphylococcus haemolyticus: daily doses of levofloxacin (750 mg) and teicoplanin (400 mg) were started.
Fever disappeared again within 3 days of antibiotics administration.
On February 5th, a vertebral biopsy on the affected bodies (L2-L3 tract) was performed as well as a bone marrow biopsy: in both tissues, both Real Time PCR and cultures gave a positive result for Non-Tuberculosis Mycobacteria (NTM) (in detail, Mycobacterium chelonae).
On February 19th, following Mycobacteria isolation, intravenous tobramicin 80 mg tid was administered together with oral clarithromycin (500 mg twice daily). Within ten days from the onset of therapy, the patient claimed to have had a significant relief from dorsal and lumbar pain.
Meanwhile (February 28th), due to the occurrence of epigastric pain with retrosternal pirosis, an oesophagogastroduodenoscopy was performed which showed a single ulcerated lesion 1.3 cm long in the great curvature of the stomach. Ulcer biopsy showed epithelioid and spindle-shaped cells with nuclear atypia and the immuno-phenotypic profile was positive for a GIST pattern: CD117, CD34, Ki67 10%.
In spite of targeted multidrug treatment, fever appeared again (over 38 °C) and on March 24th, the patient revealed acute dyspnea with blood gas analysis showing low PaO2 (60.3 mmHg) and low PaCO2 (27.4 mmHg), blood pH was 7.41. An urgent chest X-Ray showed bilateral lung reticolo-nodular infiltrates with the characteristics of an acute respiratory distress syndrome (ARDS).
Real Time PCR and O-toluidine smears for Pneumocystis Jirovecii on sputum resulted negative whereas CMV DNA was detected as being positive with 1094 UI/mL.
The patient was transferred to the intensive care unit (ICU) on the same day but, in spite of assisted ventilation and life supports, he died within 5 days of his ICU admission (Additional files and ).
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pmc-6307242-1
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A 77-year-old Japanese man with a history of hypertension and diabetes mellitus developed chest compression at rest and was referred to our hospital. On initial examination, we observed higher blood pressure, normal heart rate, tachypnea, and normal body temperature (154/94 mmHg, 80 beats per minute, 22 breaths per minute, and 36.6 °C, respectively). His first and second heart sounds had normal loudness, and a fourth heart sound was heard. Neither the third heart sound nor murmur was heard. A coarse crackle was heard in the lower field of his right lung. Electrocardiography (ECG) showed regular sinus rhythm and ST elevation in precordial leads. His value of troponin-I was 1682 pg/ml. The findings of the physical examination, ECG, and a high value of troponin-I supported the diagnosis of ST segment elevation myocardial infarction, classified into Killip classification II. Coronary angiography showed 90% stenosis of his proximal left anterior descending artery (LAD), 75% diffuse stenosis of his proximal right coronary artery (RCA), and total occlusion of his mid RCA with a Multicenter CTO Registry of Japan (J-CTO) score of 3, which originated from the septal branch (Fig. a and b). A month after PCI of his LAD, PCI of his RCA-CTO was planned because of remaining chest discomfort on effort.
In the second intervention, his serum creatinine level was 88 umol/L, and the stage of chronic kidney disease was 3A. His B-type natriuretic peptide level was 400 ng/L and left ventricular ejection fraction was 45%. Heart failure was compensated. Seven-French Amplatz 1.0 with side hall and 6-French Extra Backup 3.5 with side hall were engaged to his RCA and LAD, respectively. Septal channel tracking was performed with SUOH 03® supported by Caravel® in the manner of channel surfing. After the wire was advanced to the distal cap of the CTO lesion, Gaia Next 1® supported by Corsair® penetrated the lesion antegradely with the kissing wire technique; however, the antegrade wire was repelled by severe calcification and penetrated into the pseudolumen. Gaia Next 1® was changed to Grand Slam®. Then, a 2.5-mm balloon was delivered to the lesion and dilated. Gaia Second® was retrogradely advanced to the tip of the dilated balloon (contemporary reverse CART) (Fig. a). After intravascular ultrasound (IVUS) confirmed the retrograde wire was located in the true lumen, the wire was inserted into the antegrade guiding catheter. After externalization with RG3®, the CTO lesion was dilated with a 2.5-mm balloon. Stents were deployed from the mid to the ostium in the RCA without contrast medium, using IVUS marking and dummy wire (Fig. b). The ostium of the RCA was fully covered with the stent, and several struts protruded to the aorta, which was confirmed by IVUS. Contrast medium was injected two times after stent implantation to confirm coronary flow and no perforation (Fig. c). The total amount of contrast medium was only 8 mL for CTO-PCI. Our patient did not develop CI-AKI and his chest discomfort has disappeared (Additional file ).
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pmc-6307248-1
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A 67-year old woman with a history of mastectomy and sentinel node procedure due to breast cancer three years ago, was seen in an outpatient clinic of a non-academic hospital for progressive perioral numbness and dizziness. At first, a Cerebrovascular accident (CVA) was suspected, so treatment with carbasalate calcium 80 mg once a day was started, see timeline (Fig. ).
Despite therapy, the symptoms progressed and the patient was admitted for further analysis. The initial diagnosis of CVA in the vertebrobasilar region was rejected, because the Magnetic Resonance Imaging (MRI) showed fully intact vasculature. However diffuse white matter lesions around the fourth ventricle with extension into the pons and medulla oblongata were seen (Fig. ).
A cerebral spinal fluid (CSF) sample showed pleocytosis of 240 cells/μL with 30% lymphocytes and a glucose of 3.7 mmol/L. Blood and CSF cultures were negative. With these results, Herpes encephalitis with secondary vasculitis was considered for which acyclovir and dipyridamole was started. A second CSF sample showed pleocytosis of 102 cells/μL with 96% lymphocytes and a glucose concentration of 3.2 mmol/L. Unfortunately, the patient deteriorated, despite the initiated therapy.
At initial presentation the Borrelia serology was negative. However 15 days later the Borrelia IgG became positive with a negative IgM. Because of this unsuspected Borrelia sero-conversion, in combination with a confirmed and recent history of a tick bite, Lyme’s disease was diagnosed. Hence, intravenous therapy with ceftriaxone and dexamethasone was initiated. However after four days, the situation worsened dramatically. The patient developed spiking fever, a complete hemi-paresis and brain nerve palsy progressed. Because of the neurologic deterioration and the diagnostic impasse, the patient was transferred to an academic hospital, three weeks after initial admission.
At presentation in our center, the patient was somnolent (Glasgow Coma Scale (GCS) 14) with a complete left-sided hemiparesis. She had a fever (40.2 °C), high blood pressure (167/70 mmHg), tachycardia (100 beats/min) and tachypnea (25/min). During admission on the neurological ward, the situation rapidly worsened, so transfer to the intensive care unit (ICU) was necessary that same day. On the ICU the patient was intubated because of the risk for aspiration due to a GSC of 7 (E1M4V2), with a concomitant full left sided hemi-paresis. A new CSF sample showed mild pleocytosis of 23 cells/μL and a glucose concentration of 3.4 mmol/L.
A new interview with the family directly after ICU admission revealed important and until then unknown information: firstly, the patient appeared to be a professional cat breeder and secondly she was fond of soft French cheeses. This specific and important information had for unexplained reasons not been retrieved until then. Toxoplasmosis had already been ruled out, so Listeriosis appeared to be a likely diagnosis. Intravenous therapy with amoxicillin (2 g, every 4 h) and gentamycin (7 mg/kg once a day) was promptly initiated. Two days later, the blood cultures taken in the non-academic hospital on day 22 of the illness as well as the CSF cultures taken in the academic hospital, showed gram-positive rods, identified as Listeria monocytogenes, confirming the diagnosis. A new MRI showed diffuse hyperintensity and swelling of the basal ganglia, with enhanced ring-shaped areas that indicate necrosis (Fig. ).
Because of further detoriation, persisting GCS 3, absence of brainstem reflexes and in the absence of epileptic activity, intensive care treatment was withdrawn, for reasons of dispropriate care. The patient died a few hours later. Proxy consent for autopsy was obtained.
Autopsy revealed no signs of recurrence of breast cancer. There was focal pyogenic meningitis with a mixed nuclear inflammatory infiltrate extending throughout the Virchow Robin spaces, along the vessels, recognized as a myelo-radiculitis. There were signs of vasculitis in almost the entire brain, with complete destruction of the vessels in the basal ganglia (Fig. ). Also the midbrain showed active vasculitis with diffuse hemorrhagic infarction (Fig. ). In the right caudate nucleus some active abscesses were still visible.
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pmc-6307277-1
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A 32-year-old Colombian male, resident of an urban area, heterosexual without a stable partner. His medical record was notable for transfusion of fresh frozen plasma 4 years ago due to a consumption coagulopathy caused by sepsis secondary to perforated appendicitis. The patient consulted for 6 months of diarrhea with abundant 4 to 5 foamy, foul-smelling stools per day, no blood or mucus were present in feces. It was associated with asthenia, anorexia, and non-productive dry cough, nocturnal diaphoresis, fever and weight loss of 12 Kg (body mass index, BMI, 15.22 Kg/m2). In the last month, he presented a reddish generalized non-confluent maculopapular rash without compromise of palms and soles (Fig. ). Physical examination showed painless hepatomegaly, without other abnormalities.
A fourth-generation human immunodeficiency virus (HIV) assay was positive, and viral load was 636.000 VIH-1 RNA copies/ml, Log10: 5.80, CD4 T lymphocyte cell (CD4) count was 2 cells/mm3. Modified Ziehl–Neelsen stain in feces showed oocysts of Cryptosporidium spp, and a Multiplex Polymerase chain reaction (PCR) FilmArray test in feces identified Cryptosporidium and enteropathogenic Escherichia coli. Esophagogastroduodenoscopy and colonoscopy were performed and did not show macroscopic abnormalities; several biopsies were taken from the third portion of the duodenum, cecum, transverse and sigmoid colon; they did not reveal any abnormalities either. Serum Cytomegalovirus (CMV) viral load was negative. The patient received treatment with Nitazoxanide 500 mg PO B.I.D for three days with resolution of the diarrhea.
On admission blood cultures were taken. Fungi grew in blood cultures. A preliminary Gram stain exhibited budding yeasts, India ink test was positive for Cryptococcus spp. The blood culture final report confirmed Cryptococcus neoformans. Lumbar puncture was performed to rule out central nervous system involvement. Cerebrospinal fluid tests were taken: cytology, chemistry, routine stains, and Multiplex PCR FilmArray were negative. Induction treatment with amphotericin B at a dose of 1.0 mg/kg Q.D and fluconazole 800 mg Q.D were given for 2 weeks.
A chest X-ray and a thorax computed tomography (CT) scan showed a random distribution of micro-nodular lesions, with a preference for peripheral areas of the lungs (Fig. ). Given these findings, we decided to perform a bronchoscopy with optical fiber with findings of lesions compatible with candidiasis in oropharynx and laryngopharynx, without other lesions present in the rest of the study. The fluid extracted from the bronchoalveolar lavage (BAL) was negative for routine stains: KOH test, Gram and Ziehl Neelsen. Fungi and Mycobacteria cultures and a GeneXpert assay for Mycobacterium tuberculosis (MTB) were negative. Cytological studies of the fluid did not exhibit cellular atypia.
Other laboratory tests showed hyperferritinemia (patient value = 1000 ng/mL, reference value 23–336 ng/mL) and mild elevation of alkaline phosphatase (patient value = 152 U/L, reference value = 38–126 U/L) which raised suspicion for histoplasmosis due to the findings of hepatomegaly, skin rash and the random micronodular compromise seen in the chest images. A galactomannan antigen test for Histoplasma capsulatum was performed in urine (with enzyme immunoassay (EIA), Immuno Mycologics IMMY) and was positive with 137 ng / mL (reference value < 0.5 ng / ml), which confirmed the diagnosis of disseminated histoplasmosis. Due to these findings, fluconazole was stopped and maintenance therapy was initiated with Itraconazole 200 mg T.I.D for three days and then B.I.D at least for 1 year.
The patient had a satisfactory outcome, with resolution of his diarrhea, disappearance of his rash by the end of the induction phase, and the respiratory symptoms also improved. Patient was discharged with the indication to start HAART with Tenofovir/Emtricitabine 300/200 mg Q.D and Raltegravir 400 mg B.I.D four weeks after induction therapy.
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pmc-6307286-1
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A 21-year-old male Caucasian was referred to our Center due to a cystic formation in his LV. He is a student and lives in a house with his parents, in a rural area of the country, but they do not work in agriculture. He complained about fatigue and weakness with exertion, as well as palpitations and blurred vision. He was completely asymptomatic up until 6 months prior to his current presentation. His physical examination was unremarkable. His high sensitive troponin T and N-terminal -pro-brain natriuretic peptide were normal. His 24-h electrocardiogram was notable for non-sustained ventricular tachycardia and biphasic T waves.
Transthoracic echocardiography (TTE) revealed a multivesicular, septated cystic formation with a thin outer wall, within the basal and mid part of the IVS. The largest daughter cyst measured 6.5 × 6 cm and protruded into LV cavity (Fig. a). All the other daughter cysts protruded into the right ventricle (RV) (Fig. a). Mild inflow obstruction of the RV was present. No connections between the cysts and blood flow were observed on continuous-wave Doppler and color-flow mapping. Further workup consisted of CMR, which corroborated the TTE findings. Total lesion size was 8.2 × 7.6 × 6 cm. Residual myocardium was present only in the apical segments of the IVS, while none was observed in the affected area (Fig. b). Thoracic and abdominal imaging revealed multiple hepatic cysts. Serologic confirmation of echinoccocal infection was performed with Western blot and enzyme-linked immunosorbent assay. Based on its imaging characteristics, the cystic pathology was described as a type 2 active lesion.
Technical challenges from a surgical perspective included total removal of the cyst without disseminating its contents, as well as a potentially complex reconstruction of the IVS. Consequently, medical therapy with albendazole (dose: 15 mg/kg) was initiated. Bisoprolol and amiodarone were administered due to ventricular arrhythmia. Over the next 8 weeks, the patient was monitored closely and serial TTE examinations revealed a great reduction in total cyst size (Fig. c). Downsizing was observed in all daughter cysts, with practically complete degeneration of the largest daughter cyst. Furthermore, its content was denser and more compact, just as its outer wall was thicker. These findings were confirmed on the CMR – the size of the hydatid cyst was now 6.8 × 2.8 × 5.1 cm and the outer layer was fibrotic (Fig. d). Based on these findings the cyst was then classified as transitional, borderline inactive. We found neither imaging nor clinical evidence of cyst rupture. Nevertheless, full body checkup was repeated and no signs of spreading infection or embolism were observed. Praziquantel, in the total dose of 50 mg/kg, divided into 3 doses per day, during 14 days, was added to the therapy, after which surgery was scheduled. During this period the patient experienced an episode of sustained ventricular tachycardia accompanied by loss of consciousness.
The surgical procedure consisted of several steps. After the initiation of cardiopulmonary bypass and cardioplegic arrest, a right atriotomy was performed and the pathology could be seen through the tricuspid valve. A protrusion within the IVS was clearly visible, and corresponded to the imaging data. Initially, a purse string was placed in the fibrous wall of the cyst. Then, controlled aspiration of its fluid content was performed, which effectively reduced the size of the cyst, as well as the tension within it. The opening in the cyst was then enlarged in order to gain access to the remainder of its contents (Fig. ). The cyst was filled with multiple smaller cysts suspended in a more liquid substrate. All of these were removed, taking care not to disseminate their contents (Fig. ). Upon the removal of the substrate, pericyst was packed with 10% sodium chloride. Sponges impregnated with the solution were left in place for 15 min. The inner layer of the pericyst was destroyed with a combination of mechanical abrasion and chemical agents. The free edges of the pericyst were then resected, and the integrity of the IVS checked. The operation was completed in the standard fashion. Intraoperative transesophageal echocardiography was used to confirm IVS integrity and tricuspid valve competence. Pathological and microbiological analysis of the intraoperatively collected material confirmed the initial diagnosis.
The patient had an unremarkable postoperative course. Postoperative TTE demonstrated normal size and function of both ventricles with an aneurysm of the basal IVS but with no signs of an interventricular shunt (Fig. ). Medical therapy with albendazole was continued for three additional cycles of 28 days each, with 14-day intervals between 28-day cycles. Six weeks later, clinical and TTE examination results were unchanged. The hepatic lesions were addressed after the cardiac surgical procedure. At 6-month follow-up the patient remains well and free of disease recurrence or ventricular arrhythmia (Additional file ).
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pmc-6307304-1
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A 56-year-old woman presented to our hospital with acute congestive heart failure. She needed dobutamine support and bilevel positive airway pressure for NYHA class IV dyspnea. Chest radiography revealed congestive heart failure. Echocardiography revealed severe aortic stenosis with heavily calcific bicuspid valve; the LVEF was significantly reduced at 15%. The aortic valve area measured 0.52 cm2. Mean pressure gradient was 49 mmHg. A peak aortic jet velocity was 4.4 m/s. Right-heart catheterization revealed a cardiac index of 1.6 L/min/m2 and pulmonary hypertension with the mean pulmonary artery pressure of 55 mmHg. Coronary angiography showed normal coronary vasculature without signs of significant stenosis. The pulmonary capillary wedge pressure was 37 mmHg. Computed tomography demonstrated a mildly dilated ascending aorta with a diameter of 42 mm. She was diagnosed as heart failure reduced ejection fraction (HFrEF) due to severe aortic stenosis. The society of Thoracic Surgeons predicted mortality score was 12.4%.
Our heart team discussed her treatment. Our patient was a younger AS patient with severe LV contractile dysfunction and with bicuspid valve. Considering the severe LV contractile dysfunction, the patient seemed suitable for TAVI as the lack of ischemic cardiac arrest and extracorporeal circulation helps avoid ischemia, as well as ischemic reperfusion injury, inflammatory reaction, and oxidative stress. However, we hesitated to perform TAVI for this patient because extension of TAVI to such a younger patient with longer life-expectancy raises the issue of durability. Leaflet asymmetry of the implanted transcatheter heart valve which might occur after deployment into bicuspid valve may have an impact on long-term valve durability. While, conventional SAVR is possible while the heart is arrested with cardioplegic arrest, which is effective in majority of AS patients with acceptable morbidity and mortality. However, in some cases, especially in patients with impaired LV function like our patient, ischemic period followed by reperfusion period may lead to myocardial injury, which is associated with high perioperative mortality and morbidity. If SAVR could be performed with beating heart condition, the patient had benefited from this procedure without myocardial ischemia similar to TAVI. In spite of recent advances in myocardial protection methods, blood supply is the most effective technique of myocardial protection under beating heart condition. Cardioplegic arrest may induce reperfusion injury. In contrast, maintaining the myocardial contraction results in less myocardial edema and better cardiac function []. We therefore decided to perform on-pump beating AVR with selective antegrade coronary artery blood perfusion.
She could not lie on her back due to severe orthopnea. Therefore, percutaneous cardiopulmonary support (PCPS) was initiated at the femoral vessels before the induction of general anesthesia. Surgery was performed via a median sternotomy. Cardiopulmonary bypass (CPB) was established after central cannulation. Under systemic temperature of 35–37 °C, CPB flow rates maintained at 2.5–2.8 L/min/m2, with a mean systemic pressure 60–80 mmHg. The aorta was crossed-clamped and opened. Direct 5-Fr silicon coronary perfusion cannulas (Sumitomo Bakelite, Tokyo, Japan) were inserted into the left and right coronary ostia, and oxygenated blood was continuously perfused at 34 °C and at a rate of 300 ml/min with mean perfusion pressure of 150 mmHg. The cannulas were fixed to the aortic wall with 5–0 prolene, and they were secured by tying them to a tourniquet. The valve was a severe calcific true bicuspid valve. Calcified leaflets were removed using the usual approach. The calcifications extending to the aortic annulus were carefully removed using a SONOPET ultrasonic aspirator (Stryker, Kalamazoo, MI) and scalpel (Fig. ). (Video). After sizing the annulus, a 21-mm Regent mechanical valve (St. Jude Medical, St. Paul, MN) was placed into the aortic annulus using continuous suture technique with three 2–0 prolene sutures. The aorta was closed using the standard technique. Horizontal mattress suturing was performed for the first layer. After de-airing of the left ventricle, the aortic clamp was removed. Running suturing was performed for the second layer to ensure hemostasis. Transesophageal echocardiography was used to access septal and ventricular wall motion during surgery. The patient was weaned off CPB and PCPS under intra-aortic balloon pumping (IABP) support. Post-operative echocardiography demonstrated improved wall motion and an increase in the ejection fraction of up to 40%. She resumed a completely normal lifestyle by 3 weeks after the operation.
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pmc-6307307-1
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A 5-year-old girl was admitted to our Emergency Department after an episode of acute interscapular back pain occurring without trauma and followed by bilateral upper and lower limb weakness.
Her family history included 8 Italian members harboring the same homoplasmic m.3460G > A mtDNA (Table , Fig. ). All the family members presented headache poorly responsive to NSAIDs and, except for the girl and her mother, visual loss due to optic nerve pathology. The patient’s medical history was unremarkable.
The patient’s vital signs were normal and stable. At the neurological examination, her cognitive functions were normal. There were no cranial nerve lesions. She was unable to stand and walk and had more severe weakness in the right lower limb. She also presented weakness in her upper extremities and difficulties with fine hand movements, particularly in the right hand. The right patellar and Achilles tendon reflexes were brisk. The plantar reflex was positive in the right foot. She presented impaired bladder control. No alterations in touch or pain sensitivity were present in the trunk and limbs. No concomitant signs of infection or inflammation were present, and no such signs had been reported in the previous weeks. Analyses of CSF pressure, glucose, protein, cell count, viral PCR, and culture were normal, and oligoclonal bands were absent (see timeline of events and treatment in Fig. ). The patient underwent a spinal cord MRI; the results showed hyperintense signal alterations in T2-weighted sequences and restricted diffusion in diffusion weighted imaging (DWI) sequences in the anterior portion of the cervical and dorsal spinal cord, suggesting anterior spinal artery territory involvement (Fig. ). Computed tomography angiography (CT) imaging showed no arterial dissection or other vessel abnormalities. Visual evoked potentials were normal. Somatosensory evoked potentials in both legs showed decreased conduction velocities. Motor evoked potentials showed lower amplitude for cortical derivation, prolonged latency in the upper limbs and normal in the lower limbs. Central conduction time was increased in the upper limbs and normal at the lower limbs. Complete autoimmunity and thrombophilia screening were unremarkable. Testing for anti-AQP4 antibodies was negative, and anti-MOG antibodies were not significantly elevated. A cardiologic consultation and echocardiography identified normal heart and aorta features. At the ophthalmological assessment, pupillary reactions were normal, the fundus oculi did not reveal pathological signs, and color vision was not affected. The visual acuity was 9/10 bilaterally. The digital visual field test displayed a mild defect in the peripheral portion of the visual field that was more evident in the left eye. Optical coherence tomography, visual evoked potential and electroretinograms were normal. As the child grows, her visual function will require careful monitoring, particularly when she reaches the adolescence.
After obtaining written informed consent consistent with the principles set forth in the Declaration of Helsinki, total DNA was isolated from the patient’s peripheral blood according to standard protocols. Full-length mitochondrial DNA sequencing was conducted according to a previously described protocol [], and detected the haplogroup H27 was detected in the proband. The following variants were detected in the homoplasmic state: m.41C > T, m.73A > G, m.263A > G, m.1438A > G, m.3460G > A, m.4769A > G, m.8860A > G, m.11719G > A, m.15326A > G, m.16129G > A, m.16316A > G, m.16519 T > C. Based on the presence of the m.11719G > A and m.16316A > G nucleotide variants, the patient is predicted to belong to the H27 haplogroup. The m.3460G > A transition, a major mutation associated with LHON, was verified in blood-derived DNA of other family members by PCR-RFLP analysis.
Acetylsalicylic acid was administered at low doses (2.5 mg/kg daily), and high doses of methylprednisolone (20 mg/kg daily) were empirically administered for three days. Although no proven treatments for LHON are available, early treatment with idebenone is thought to limit the progression of the disease; the patient was administered 45 mg of idebenone three times daily. Within two days following this therapy, clinical manifestations improved, and the patient regained bladder control and the ability to ambulate; within one week, the girl also recovered nearly normal strength in both arms. A control spinal cord MRI together with 1H-MRS to study the lactate peak was performed 10 days after hospital admission; the results showed complete regression of the alterations and no abnormal metabolites (Fig. ). The patient continued outpatient rehabilitation, and her motor functions improved, resulting in an almost completely normalized neurological examination after 2 months and preserving these achievements at follow-up one year later.
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pmc-6308139-1
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A 53-year-old male with a posttraumatic incomplete spinal cord injury (AIS D, sub C4) was examined during his neurological rehabilitation at the Spinal Cord Injury Center at Balgrist University Hospital, Switzerland. The study was approved by the “Kantonale Ethikkommission Zürich” (EK-04/2006 / PB_2016-02051, clinicaltrial.gov number: NCT02138344) and written informed consent for publication was obtained from the patient.
The patient presented clinically with a central cord syndrome, and at-level neuropathic pain with mechanical allodynia (i.e., brush allodynia) on both forearms. Light touch was normal within the cervical segments, and sharp dull discrimination was preserved while the intensity of the pinprick stimulus was only mildly attenuated. The upper extremity motor score (left: 11/25, right: 11/25) showed a profound weakness of elbow extensors, and no voluntary muscle activity in the finger flexors and abductors bilaterally. The lower extremity motor score was normal (left: 25/25, right: 25/25). Biceps and brachioradialis reflexes, as well as knee-jerk and ankle-jerk reflexes were bilaterally exaggerated. The Babinski sign was negative. Muscle tone was normal without signs of spasticity. Coordination and gait showed discrete signs of ataxia. Magnetic resonance images revealed a multi-segmental (C5-C7), longitudinal “snake eye” appearance myelopathy (Figure ). Ulnar somatosensory evoked potentials (SEPs) and sensory nerve conduction studies were normal (Figure ).
The CHEP recording was performed according to an established protocol (, ). Noxious mechanical stimuli were applied with a 256 mN pinprick stimulator (MRC Systems, Heidelberg, Germany). Stimulus application was performed in a slow fashion in order to favor recruitment of A-delta fibers (). The skin was stimulated 20 times from a distance of 1 cm within 1 s. The experimenter was trained prior to the experiment to guarantee the stimuli are uniformly applied.
CHEPs were normal at C4 and T4 with high pain ratings to the heat stimulation, but almost complete loss of painful heat sensation and absent CHEPs at the level of C6 (Figure ). In contrast, PEPs remained preserved at all segments (Figure ).
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pmc-6308315-1
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An 80-year-old white male was referred to our endocrinology outpatient clinic in December 2015 for a fracture of the left radial head, hypercalcemia (11.9 mg/dL; normal range 8.1–10.4 mg /dL), increased PTH (681 pg/ml; normal range 15–65 pg/mL), and increased alkaline phosphatase (375 U/L; normal range 40–130 U/L). Medical history was positive for hypertension and benign prostatic hyperplasia. Physical examination, including that of the cervical region, was overall normal but a 2-year history of bone pain, muscle weakness, and nephrolithiasis was noted. Renal (CKD-EPI 87, 1 ml/min/1.73 m2) and hepatic functions were normal (Table ), as well as cardiovascular function. His medications included valsartan, alfuzosin, and cholecalciferol.
Neck ultrasound revealed a 9–mm, hypoechoic mass behind the right lobe of the thyroid gland (Figure ). Technetium 99m (99mTc)-sestamibi scintigraphy showed a focal area of increased uptake (Figure ), corresponding to the ultrasound finding, thus suggesting a parathyroid adenoma. A diagnosis of primary hyperparathyroidism due to a parathyroid adenoma was, therefore, established. A parathyroidectomy was offered to the patient, but refused. In January 2016 we thus began medical treatment with cinacalcet, starting at a dose of 30 mg twice a day. This dosage was gradually increased, in the following months, to 60 mg 3 times a day as to normalize the serum calcium levels (Figure , left panel; Table ).
In June 2017, 1 month after reaching a daily dose of 180 mg, the patient was admitted to the emergency room for tetany. Laboratory testing showed hypocalcemia (6.27 mg/dL), normal PTH (53.6 pg/mL), hypophosphatemia (2.7 mEq/L, normal range 3.5–5.5 mEq/L) and still increased alkaline phosphatase levels (411 U/L). Renal and hepatic functions were not impaired (Table ). He was treated with intravenous calcium gluconate, and stopped cinacalcet treatment.
Serum calcium, surprisingly, did not rise after cinacalcet cessation, remaining around values of 6 mg/dL for about 10 days (Figure , arrow). Neck ultrasound confirmed the presence of a hypoechoic, irregular mass behind the thyroid right lobe, this time 17 mm in diameter. An ultrasound-guided fine needle aspiration of this lesion was performed. Cytological examination revealed basophilic amorphous material, neutrophils (Figure , black arrow), macrophages (Figure , white arrow), and lymphocytes (Figure , arrowhead), consistent with necrosis and inflammation. The patient was given calcium supplement (calcium carbonate, 1,000 mg twice daily) and 1,25 dihydroxyvitamin D3 (calcitriol, 0.5 μg once per day). Three months later, serum calcium normalized and PTH remained normal (44.0 pg/ml) (Figure ). Neck ultrasound performed at the same time no further identified the parathyroid lesion (Figure ). Repeated 99mTc-sestamibi scintigraphy showed a minute area of increased uptake, which we interpreted as a remnant adenoma, although a local inflammatory reaction could not be excluded (Figure ). We gradually decreased calcium treatment to a dosage of 500 mg/die and eventually stopped it in March 2018, whereas we continued calcitriol therapy (0.5 μg once per day). At the time of our latest assessment (July 2018), calcium (9.12 mg/dL), PTH (61.9 pg/mL), and alkaline phosphatase (79 U/L) were in the normal range (Table ), clinical conditions were satisfactory except for the muscle weakness which did not improve significantly.
The above described findings suggested that the remission of primary hyperparathyroidism was caused by the apoplexy of the parathyroid adenoma.
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pmc-6308901-1
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A seven-year-old boy presented with a history of difficulty in night vision for the past five years. He was the older twin, born at term with normal birth history and developmental milestones. Family history was unremarkable and physical examination was normal. His best corrected visual acuity was 20/20 in both eyes. The anterior segment examination was normal in both eyes. The other twin had no ocular complaints and his fundus examination was unremarkable.
Dilated fundus examination of both eyes revealed a golden sheen over the posterior pole, suggestive of the Mizuo-Nakamura phenomenon (Figure 1A,B ). This sheen disappeared after 45 minutes of dark adaptation (Figure 1C,D ). There was no evidence of bone-spicules pigmentation and the optic disc and arterioles were normal. A clinical diagnosis of Oguchi’s disease was arrived at. The electroretinogram (ERG) of both eyes showed the characteristic negative waveform morphology with non-recordable single flash rod response, negative-positive combined response and normal photopic response (Figure 2 ), thereby confirming the clinical diagnosis. The nature of the disease and need for family screening were explained. Genetic testing was offered but declined by the family. At ten-month follow-up, his visual acuity, ocular and ERG findings were stable compared to the first visit.
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pmc-6308902-1
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A 73-year-old Caucasian male with a history of hypertension, diabetes mellitus, and coronary artery disease was referred to our retina department with bilateral vision loss. His medications included klopidogrel, ramipril, amlodipin, atorvastatin, gliclazide, and metformin all of which he had been using for a prolonged period. After fundus fluorescein angiography and optical coherence tomography, he was diagnosed with a ciliary artery occlusion in the left eye with a visual acuity of 20/200. The right eye was found to have an occult choroidal neovascular membrane with subretinal fluid, and so three monthly intravitreal RAN injections were performed. After the third injection, his best-corrected visual acuity (BCVA) improved from 20/32 to 20/25 in association with a decrease in central macular thickness. Two weeks after the second intravitreal RAN injection, he complained about a generalized, excessively pruriginous skin eruption on the trunk, lumbar region, and extensor aspects of the upper and lower extremities. The lesions worsened after the third injection. Laboratory examinations showed mild hyperlipidemia (cholesterol: 241 mg/dl, triglyceride: 256 mg/dl), a blood glucose of 155 mg/dl and HbA1C of 6.6%. In dermatological examination, he had a generalized, erythematous rash with umblicated papules, many of which had ridge-like borders and some contained keratin plugs (Figure 1 ). A skin biopsy of a nodule demonstrated a cup-shaped depression of the epidermis associated with a keratin plug containing compact ortho- and parakeratosis with granular nuclear debris. Altered collagen fibers were seen in the underlying dermis, with focal extrusion through the epidermis (Figure 2 ). Based on clinical and histological findings, he was diagnosed with acquired reactive perforating collagenosis (ARPC). A challenge test was considered significant as the rash and pruritus started after the injections. Because of a poor response to topical steroids, 22 sessions of NBUVB therapy were administered to obtain relief from itchy skin. Treatment for CNVM was switched from RAN to aflibercept injection administered according to PRN regimen and 3 doses were required within 13 months. No relapses of the ARPC occurred the subsequent year. Final visual acuity was 20/25 and the central macular thickness was 189 µm (Figure 3 ).
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pmc-6309058-1
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A 23-year-old woman with binocular vertical diplopia, bilateral ptosis (which worsened with left and down gazing), dysarthria, and dysphagia visited the outpatient department. She had received a primary HPV nine-valent vaccination 2 months prior and a second vaccination 5 days before the visit. The symptoms occurred on the 3rd day after the second vaccination. The muscular strength of her upper and lower extremities was normal, and the deep tendon reflex of both sides was normal. Her ptosis and diplopia temporarily improved with an ice pack and pyridostigmine test. The repetitive nerve stimulation (RNS) did not reveal a significant decrement in deltoid, abductor digiti minimi, flexor carpi, and orbicularis oculi muscles. The serum AChR antibody titer was 1.66 nmol/L. Other autoimmune disease tests, including rheumatoid factor and antinuclear antibody, were negative. A thyroid function test was normal, and no thymus abnormality was observed on chest computed tomography (CT).
She was diagnosed with MG, and pyridostigmine oral administration and high-dose intravenous steroid therapy were initiated. Her dyspnea became more severe on the 2nd day after admission, and oxygen saturation decreased; therefore, she received intravenous immunoglobulin therapy. Afterward, spontaneous breathing became more difficult, and the dysphagia and bilateral ptosis worsened. These symptoms were determined to demonstrate an MG crisis, and mechanical ventilation was initiated after endotracheal intubation (Fig. ). Although muscle strength was normal at admission, the extension power of the distal fingers decreased.
On the 7th day after admission, sudden tachycardia was observed, the patient experienced persistent pressure in the right chest, and oxygen saturation decreased during mechanical ventilation. Chest CT revealed a low-density-filling defect of the pulmonary artery in the right lower lobe. Ischemic changes in the lung parenchyma and an increased D-dimer level (2199 ng/mL) were also observed. Therefore, heparin treatment was initiated owing to the possibility of pulmonary embolism. The D-dimer level decreased to within the normal range (99 ng/mL) in the 2nd week after the increase.
In the 4th week of hospitalization, the symptoms further improved such that she could walk and the AChR antibody titer decreased (0.99 nmol/L). However, right eye ptosis and binocular vertical diplopia persisted. She was discharged after the dysphagia had completely resolved. The AchR antibody titer was normal (0.05 nmol/L) at discharge. The patient has returned to daily life without symptom recurrence or further treatment.
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pmc-6309064-1
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A 74-year-old female presented at our headache clinic with a 2-year history of headache that felt cold in the symptomatic area, which was confined to an ellipse 3 cm in diameter in the left parietal region. The headache consisted of stabbing pain of mild intensity. The episodes of pain lasted approximately 3 to 5 min each and occurred 2 to 3 times every week, with the intensity fluctuating around 2 to 3 on a 10-point visual analogue scale (VAS). There were no other complaints and no related focal neurological symptoms. The patient had no known family history of migraine, stroke, psychiatric disorders or dementia. She had a 5-year history of Type 2 diabetes. She had no cutaneous abnormalities in the painful area and had normal routine blood analyses, erythrocyte sedimentation rate and cerebral computed tomography. During the course of diagnosis and treatment, the patient’s headaches had occurred 4 times in the same area, and she complained of a cold sensation in the symptomatic skin. The symptomatic area was colder than the normal area, as estimated by touch and measured by an infrared thermometer. The recorded temperatures are presented in Table . As of a two-week follow-up visit, the patient had achieved good relief with gabapentin.
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pmc-6309064-2
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A 46-year-old male driver visited our outpatient headache clinic and complained of a twenty-year history of focal episodic pain located in a circumscribed area on the right temple. We learned that this patient had no personal or family history of migraine, stroke, hypertension or psychiatric disorders. The patient’s neurological examination was normal, with neither tenderness nor trophic changes inside the painful area. Blood tests and an MRI scan of the brain were also normal. The patient complained of an occasionally annoying hot sensation that appeared in the symptomatic area every time the pain attacked. Other than minor benefits from acupuncture and gabapentin, the intensity of the pain did not change with time. During the man’s visit to our clinic, we tested his scalp temperature using an infrared thermometer and recorded the results. We followed up with the patient over the next month and recorded the temperature the of the symptomatic area; here, we have opted to report only the records from the four most recent time points (Table ).
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pmc-6309064-3
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A 38-year-old female patient complained of a two-month history of headache; the painful area was perfectly circular and confined to a diameter of approximately 3 cm on the posterior occipital part of the head. The pain was pulsating, sometimes stabbing, with the intensity fluctuating around 5 on a 10-point VAS. The attacks of pain differed in duration, sometimes lasting 5 min and sometimes lasting a whole day; fortunately, the intensity of the pain did not affect the patient’s life quality and did not cause a mood disorder. In addition, the patient complained that she had a hot sensation in the symptomatic area every time the pain attacked, particularly in the summer, and she could feel an obvious distinction between the symptomatic area and normal areas by touch. We tested the symptomatic area with an infrared thermometer and recorded the temperature every time when the patient visited our outpatient headache office. We reported the last four data points in Table 3. However, she had no other accompanying symptoms and no related focal neurological symptoms. She had a few years’ history of alcohol intake. She had no related family history of stroke, migraine, heart disease or psychiatric disorders. In the two months preceding her visit, the patient was given acupuncture and ibuprofen, which elicited a good response, but the frequency of the attacks did not change. The patient needed to take medicine or undergo acupuncture treatment whenever the pain attacked. The patient’s neurological examination was normal, with neither tenderness nor trophic changes in the painful area. Blood tests and an MRI scan of the brain were also normal.
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pmc-6309162-1
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Patient 1 (P1), who was an 8-year-old female, was born as the third child of a Mexican mestizo family with a past history of an older sister who died before the age of 5 due to Mycobacterium and Candida infections after suffering from disseminated BCG disease from a BCG vaccine (). The mutation causing the immunodeficiency in the offspring of the family was traced to the IL12RB1 gene, which encodes the beta-1 chain of the IL-12/IL-23 receptor, with no expression of the protein in the affected homozygous children (Figure ) (). The homozygous mutation in IL12RB1 (1791+2 T>G) was determined at birth in P1 by genomic DNA sequencing of a cord blood sample. P1 received vaccines for hepatitis B, DPT, measles, mumps, and rubella without any adverse effects, but she did not receive the BCG vaccine and grew healthy without suffering infections. When P1 was 8 years old, she had a mild oral C. albicans infection, which was treated and controlled with topical nystatin. Following a second episode of oral candidiasis, she was treated with the IgG mouthwash procedure as described below.
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pmc-6309162-2
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Patient 2 (P2) was an 8-year-old girl diagnosed with a heterozygous de novo T385M missense mutation in the STAT1 gene that was previously reported as a GOF mutation (Figure ) (). P2 had recurrent and persistent oral Candida infections beginning at 8 months of age. She had received multiple drug treatments with fluconazole, nystatin, ketoconazole, and miconazole, with only partial improvements lasting from one to 3 weeks. At 8 years of age, after receiving unsuccessful treatments for oral candidiasis with nystatin and ketoconazole, she presented with severe oral candidiasis and was treated for 12 days with polyvalent IgG mouthwash.
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pmc-6310503-1
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A 46-year-old woman was hospitalized in July 2017 complaining of abdominal discomfort and fever of 2-days duration. She had no family history of malignancy. On physical examination, the patient showed abdominal distention and tenderness, and rebound pain. Abdominal examination also revealed a hard mass in the pelvic cavity, about 10 cm in diameter, located to the upper right of the uterus. Other physical findings were within normal limits. Laboratory evaluation showed raised levels of serum amylase (6713 U/L, normal <110 U/L), CA125 (>1000 U/mL, normal <35 U/mL), and CA19–9 (>1200 U/mL, normal <37 U/mL). Computed tomography (CT) of the abdomen and pelvis revealed a solid mass with uneven density in the pelvis (Fig. D). However, the CT scan showed a normal image of the pancreas (Fig. A–C). Based on the overall findings, especially her abdominal pain and raised amylase, acute pancreatitis was suspected and the patient received appropriate therapy, including fasting, decompression, anti-infective treatment, inhibition of pancreatic secretion, and electrolyte balance. Once her symptoms had disappeared, she underwent surgery to obtain a definite diagnosis and to resect the tumor. Laparotomy revealed a tumor mass originating from the right ovary, with a maximum diameter of 12 cm, and a normal pancreas. The patient underwent hysterectomy, bilateral salpingo-oophorectomy with omentectomy, and appendectomy. The pathology results showed advanced serous papillary ovarian carcinoma (Fig. ). Immunohistochemical examination of the carcinomatous component showed positive immunostaining for p16, Pax-8, p53, progesterone and estrogen receptors, and Ki-67 (60%). The Figo staging of this case is IB.
Four days later, her blood serum amylase dropped back to the normal. Two weeks later, she received 5 courses of chemotherapy with paclitaxel and carboplatin. Her chemotherapy was completed in December 2017 and her CA125 level returned to within the normal range. However, her serum CA125 levels rose again (172.2 U/mL) in January 2018, before the 6th course of chemotherapy, and CT of the abdomen and pelvis revealed multiple abnormal-density lesions in the peritoneum and pelvic cavity. We considered these to be metastases, and the patient was deemed unresponsive to her previous chemotherapy. She was therefore changed to a chemotherapy regimen containing gemcitabine and capecitabine, and remained on this regimen at the time of writing. The patient has provided informed consent for publication of the case.
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pmc-6310506-1
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Case 1: A 58-year-old man visited our hospital for paroxysm, progressive declines in memory and cognition and slow response for the first time in 2011. The patient had a long course of illness and showed a progressive tendency, with refractory hypoglycemia and no history of hypertension. The onset of hypomnesis, dysuria, and dry stools began in 2009. In 2010, the symptoms of dry skin, no sweat, paroxysmal fever, fatigue, and unstable walking appeared. During this period, the patient had a plantar sensation and paresthesia and was misdiagnosed as “viral encephalitis” and “immune encephalitis”. There was not any similar history in his family.
Several times of magnetic resonance imaging (MRI) plan scan (Fig. ) were performed in our hospital, revealed the changing process of the disease. There was no obvious abnormal signal or lesions in the early stage in 2011 and 2012. The subcortical linear hyperintensities in DWI appeared in 2014, predominantly in the frontal lobes, secondly in the occipital lobe, corresponding with hyperintensities in fluid-attenuated inversion recovery (FLAIR) images. The abnormalities in the frontal lobes spread along the corticomedullary junction as the disease progression but did not expand into the deep white matter even in the latest MRI scan. On the contrast, the hyperintensities in DWI and FLAIR images in the occipital lobe disappeared 5 years after onset, together with the T2 weighted images hyperintensities.
Finally, the skin biopsy of patient 1 was performed and the tissue was taken from the 10 cm superior of the lateral malleolus and sectioned in 6 μm thickness. The diagnose of NIID is more obvious by finding anti-ubiquitin staining in nuclear (Fig. A). The patient is receiving symptomatic treatment in our hospital and the symptoms are relieved.
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pmc-6310506-2
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Case 2: A 60-year-old female patients visited our hospital for symptoms of walking instability, dizziness, headache, poetic language, blurred vision, bucking, difficulty swallowing lasting for 5 months. After receiving symptomatic treatment in the local hospital, these symptoms got worse. The specialty check-up of our hospital showed that the patient was conscious, with a slow gait, vague speech, degenerated muscle strength, decreased muscle tension and normal tendon reflex. And the laboratory examinations were all within the normal limit. There was no similar history of her family.
Comprehensive MRI inspections were done at our hospital. MR images showed a mild degree of cerebral atrophy, with a slight widening of the hemispheric sulci. High-intensity lines along with corticomedullary junction appeared symmetrically in DWI images (Fig. B–C) together with the T2 weighted images and FLAIR hyperintensities (Fig. A). There was no abnormality in gadolinium-enhanced images or 3D time-of-flight images or the series of susceptibility weighted imaging. The cerebral blood flow of the left frontal lobes is slightly decreased compared with the right part. The peak value of Cho, NAA or Cr in MR Spectroscopy had no obvious abnormity.
The skin biopsy of patient 2 was carried out. Hematoxylin-eosin staining showed intranuclear inclusions in the specimens of the second patient (Fig. B). The diagnose is NIID. The patient is receiving symptomatic treatment in our hospital and the symptoms are relieved.
The patients provided written informed consent for reporting the case details. In this case, the patient accepted the standard, proven diagnosis, and therapy in the Department of Neurology, so ethical approval was not necessary.
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pmc-6310510-1
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A 53-year-old female patient was admitted to our hospital with chief complaints of epiphora, discharge, eyelid flare up, and swelling near the inferior lacrimal punctum in the left eye, all of which had developed 6 months earlier. Based on the aforementioned symptoms, the patient was initially diagnosed with bacterial conjunctivitis at a local ophthalmologic clinic and administered antibiotic eye drops (0.5% levofloxacin, 4 times daily) for 6 months. However, her symptoms did not improve, and they had worsened 2 weeks prior to her admission. Subsequently, she was diagnosed with chronic dacryocystitis at a local ophthalmologic clinic and transferred to our hospital for recommended surgical treatment. The Institutional Review Board/Ethics Committee of Bucheon St Mary's Hospital approved this study. It was performed in accordance with the tenets of the Declaration of Helsinki. Written informed consent was obtained from the patient for publication of this case report and accompanying images.
The patient had hypertension (blood pressure, 145/90 mm Hg), but no other specific underlying disease or history of previous surgery. On admission, her corrected visual acuity in both eyes was 1.0 and the intraocular pressure was normal. Slit lamp examination results showed conjunctival congestion in the inner corner of the left eye, eyelid flare up, swelling near the inferior lacrimal punctum, and yellowish discharge from the punctal orifice (Fig. ).
There was no punctal regurgitation observed during the lacrimal sac compression test and the lacrimal irrigation test, which was performed using saline through the upper lacrimal punctum. Based on the lack of abnormal findings in the lacrimal system patency test, nasolacrimal duct obstruction, and chronic dacryocystitis could be ruled out. However, based on the yellowish discharge and concretion observed in the lacrimal punctum when the lower lacrimal punctum was squeezed using a cotton-tip applicator, a diagnosis of primary canaliculitis was made (Fig. ).
Following the diagnosis of primary canaliculitis, 1-snip punctoplasty and canalicular curettage, using a 1-mm diameter chalazion curette, were performed, and lesions, such as concretions and debris, were completely removed (Fig. ). The surgery was completed after performing the lacrimal irrigation test to verify no abnormality in the patency of the lower lacrimal system. The specimens from the lesions were sent to the laboratory for microbiologic culture and histologic examination. The microbiologic culture test could not identify the exact causative organism, but gram-positive rods were found; meanwhile, the histologic examination identified tangled clumps of filamentous organisms, which were findings consistent with a diagnosis of sulfur granules. After the surgery, the patient was prescribed oral antibiotics (cefditoren pivoxil 100 mg, 3 times daily) for 2 weeks, along with four antibiotic eye drops (0.3% gatifloxacin, 4 times daily) for 4 weeks.
After the surgery, the patient's initial symptoms, which had caused discomfort, showed improvement, but the symptoms of epiphora and yellowish discharge from the lacrimal punctal orifice were observed during an outpatient follow-up visit 2 months after the surgery (Fig. ).
Based on the diagnosis of recurrent primary canaliculitis, 4-snip punctoplasty and canalicular curettage were performed. Using the method described by Kim et al in a case of severe punctal stenosis,[ 4-snip punctoplasty was performed with local infiltrative anesthesia on the conjunctiva below the punctum using 2% lidocaine with 1:100,000 epinephrine. Following this, a punctal dilator was used to dilate the punctum and then the 1st vertical cut was made in a downward direction along the ampulla using Vannas scissors. Subsequently, a 2nd horizontal cut, approximately 2 mm long, was made along the roof of the canaliculus, and a 3rd vertical cut extending from the edge of the 2nd cut, was made to form the flap. Lastly, the base of the flap was removed to create a rectangular-shaped opening.
Next, canalicular curettage was performed using a 1-mm diameter chalazion curette, and lesions such as concretions and granuloma were completely removed. The surgery was completed by performing a lacrimal irrigation test to verify no abnormality in the patency of the lower lacrimal system. The specimens from the lesions were sent to the laboratory for microbiologic culture and histologic examination (Fig. ).
Gram-positive rods were found; however, the microbiologic culture test could not identify the exact causative organism. Additionally, tangled clumps of filamentous organisms—findings consistent with a diagnosis of sulfur granules—were found in the histologic examination.
After the 2nd surgery, the patient was prescribed oral antibiotics (cefditoren pivoxil 100 mg, 3 times daily) for 2 weeks along with 4 weeks of antibiotic eye drops (0.3% gatifloxacin, 4 times daily).
One month after the 2nd surgery, a well-formed punctum was observed, and all signs of epiphora, discharge, eyelid flare up, and swelling near the inferior lacrimal punctum in the left eye had disappeared (Fig. ).
There were no findings of recurrence or complications during the subsequent 6-month follow-up period.
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pmc-6310519-1
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A 48-year-old Caucasian man presented to the Neuro-Ophthalmology Department of the Rothschild Ophthalmic Foundation in June 2016 for decreased vision, transient visual obscuration, pulsatile tinnitus, and headaches. His symptoms had been progressively worsening for the previous 7 months. The patient was a pharmacist and was not overweight. He had a history of UC in 2002 that was diagnosed during the workup of chronic diarrhea. The patient did not have any medication for UC. He did not smoke, nor did he use recreational drugs. On examination, best-corrected visual acuity was 20/40 OD and 20/20 OS. Eyelid examination was unremarkable. The pupils were equal and reactive. There was no relative afferent pupillary defect. Ocular movements were full and he was orthophoric in all gaze directions. Dilated fundus examination showed retinal folds between the macula and the optic disk and bilateral grade-2 optic disc swelling (Fig. ). Visual field testing revealed enlarged blind spots and diffusely decreased visual field sensitivity in both eyes (Fig. ). Ocular ultrasonography revealed enlarged optic nerve sheaths. Brain MRI ruled out brain tumor and venous thrombosis. There were signs of ICH including empty sella and bilateral lateral venous sinus stenosis. Lumbar puncture showed CSF opening pressure of 26 cm of water with normal CSF contents. The headaches persisted after lumbar puncture. Ancillary testing did not reveal vitamin A deficiency or anemia. Idiopathic ICH was suspected. The patient was treated with a daily dose of 1000 mg of acetazolamide that was gradually tapered. Headaches initially improved but the treatment could not be decreased under 750 mg a day without recurrence of the symptoms.
Extensive review of systems showed that patient still had chronic diarrhea. Because of the history of UC, a colonoscopy was performed in June 2017 and showed active proctitis. Fecal calprotectin level, which has been shown to be correlated to acute inflammation in intestinal inflammatory diseases, was increased to 1755 μg/mg (normal range: 10–50 μg/mg). In September 2017, he was given oral mesalazine, 2000 mg a day. UC symptoms quickly resolved, and fecal calprotectin decreased to 7 μg/mg. Symptoms of ICH and papilledema resolved in September 2017. Acetazolamide was progressively tapered over the course of the 9 subsequent months and the patient did not show any worsening of symptoms or papilledema. In September 2018, 1 month after acetazolamide withdrawal, visual acuity was 20/20 on both eyes and visual fields were full. There remained macular folds that caused metamorphopsia in the right eye. Brain MRI showed resolution of empty sella but there was persistence of bilateral lateral venous sinus stenosis.
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pmc-6310524-1
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A 53-year-old woman underwent consultation at a local clinic for arthralgia. Continuous cardiac murmurs were detected at the left upper sternal border region and dyspnea on effort that gradually exacerbated. She was referred to the cardiothoracic department at the university hospital in the same city. Her height and body weight were 153 cm and 67 kg, respectively. Chest radiography revealed increased pulmonary vascular shadow and cardiomegaly. Electrocardiography showed left ventricular hypertrophy. Transthoracic echocardiography (TTE) demonstrated left atrial (LA) and left ventricular (LV) dilatation. The LA volume was 85 mm, and the LV end diastolic dimension was 58 mm. Dilated ascending aorta with mild aortic regurgitation and mild mitral valve regurgitation were observed. In addition, TTE revealed the presence of a PDA with continuous flow observed from the descending aorta to the pulmonary artery (PA). The estimated pulmonary to systemic ratio (Qp/Qs) was 1.2.
Contrast-enhanced 3D computed tomography (CT) helped to determine the anatomical details around the PDA (Fig. ). It revealed a conically shaped duct with calcification at the aortic end (Fig. ). PDA with calcification at the aortic end was 14 mm in diameter, arising from the descending aorta, and was 30 mm distal to the left subclavian arterial (LSCA) orifice on the lesser curvature side.
PDA closure devices, such as the Amplatzer duct occluder (AGA Medical, Golden Valley, MN) or coil embolization, were deemed too risky for this patient. These percutaneous interventions have potential risks because friable tissue due to aneurysmal change, calcification, and the morphology of the PDA, may result in severe complications such as device migration, rupture, or residual shunt. Open surgery also carries a high risk because cardiopulmonary bypass (CPB) is required due to calcification. We decided to use a stent graft, which is usually used for treating thoracic aortic diseases.
TEVAR was performed in a catheterization laboratory under general anesthesia. Aortography before stent graft implantation demonstrated that most of the contrast agents ran into the PA through the PDA. A tapered stent graft (S&G, Bio 34–30 mm × 110 mm, Korea) was used. The patient had an adequate proximal landing zone, including the LSCA orifice. Half of the LSCA orifice was covered. A stent graft was successfully implanted. Aortography immediately after stent graft implantation revealed complete occlusion of the PDA. No endoleaks were observed. The procedure was completed in 75 minutes.
The patient's postoperative course was uneventful and she was discharged on the 9th day after surgery. There were no complications, such as left arm claudication or vertebrobasilar insufficiency, either after the operation or during the follow-ups. CT was conducted at discharge (Fig. ) and once a year after the procedure. Follow-up CTs have shown no other vascular complications such as endoleak or fistula, and the patient is doing well.
The Human Research Ethics Committee of Yeungnam University Hospital waived the requirement for approval as this is a single-case report. The patient provided written informed consent for publication of clinical details and images.
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pmc-6310526-1
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A 71-year-old woman was admitted to our hematology department complaining of swelling with pain, skin redness, and increasing skin temperature in the right hip. There was no history of physical or psychological diseases, alcohol abuse, or familial history of similar diseases. Physical examination showed a red mass in the right hip and a long strip of mass in the right groin area; however, no superficial lymph nodes were found. Moreover, there was no enlargement of the liver or spleen. The patient was initially diagnosed with local infection and prescribed cephalosporin which had no obvious beneficial effects.
Subcutaneous puncture of the right buttock suggested that lymphoid tissue had hyperplastic lesions. Abnormal cells were found in the bone marrow, which suggested that lymphocyte bone marrow infiltration was considerable (Fig. A). Right groin area lymph node biopsy pathology results showed that abnormal hyperplastic lymphoid tissue invasion was visible, the nucleus of the hyperplastic lymphoid cell was irregularly shaped, the germinal center was atrophied, and the lymphoid structure was distinct from normal lymphoid tissue (Fig. B). The immunohistochemistry results of the right buttock tumor and right groin area lymph nodes were positive for CD5 (weak positive), CD20, CD21, CD23, and Bcl-2, but negative for CD3, CD10, and cyclin D1 (Table , Fig. ). These results suggest that the buttock tumor and abnormal lymph nodes were both non-Hodgkin marginal zone B cell lymphomas.[ positron emission tomography/computed tomography (PET/CT) scans showed increased non-uniform fluorodeoxyglucose (FDG) uptake, with standardized uptake values (SUV)max of 11.6 in the subcutaneous tissue of the right buttock, SUVmax of 9.1 in the right gluteal muscle space, and SUVmax of 9.9 in multiple nodules on the right pelvic wall and right inguinal region (Fig. ). With respect to tumor aggressiveness in the same side of the diaphragm, the disease was considered to be PE-NHL of Ann Arbor stage II.[ The patient was subsequently treated with 4 courses of rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy. Comparison of the PET/CT scans before and after treatment showed that the lesion had decreased, as had FDG-uptake in the subcutaneous tissue of the right buttock, with SUVmax of 11.6 vs 2.5, respectively (Fig. ).
The patient was followed up for 3 months. The hip lesions had significantly narrowed with skin color deepening, and the pain was gradually relieved. Subsequently, no relapse or distant metastasis has been detected.
The patient provided informed consent. The study design was approved by the appropriate ethics review board and was CARE compliant.
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pmc-6310537-1
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A 57-year-old man with cough and minimal whitish expectoration was diagnosed with adenocarcinoma after a biopsy was conducted on the upper lobe mass of his left lung on March 4, 2016. Mutational analysis revealed that he lacked EGFR mutations or ALK gene rearrangements. CT scans showed that this patient had developed multiple metastases, including mediastinal and hilar lymph nodes, and also to the right intrapulmonary lymph nodes. He received 6 cycles of Pem-Cis chemotherapy, followed by thoracic radiation. Review of the CT scan at completion of sequential chemoradiotherapy treatment resulted in a significant shrinkage in the primary tumor in his left lung, while simultaneously resulting in a slight increase in metastatic lymph nodes (Fig. ). In February 6, 2017, CT scans showed that the tumor progressed rapidly. He was then scheduled to receive gemcitabine plus nedaplatin (Gem-Ndp) chemotherapy. However, the patient had to discontinue the planned 2nd cycle of this regimen as he developed moderate pneumonia. After systemic antibiotic treatment, the patient improved symptomatically and became increasingly energetic. However, CT scans on March 29 revealed that his tumors had progressed further. Owing to his poor physical condition after Gem-Ndp treatment, the chemotherapy regimen was changed to Pem-Cis. However, CT scans on May 11 failed to detect any shrinkage in his tumor. In addition, lymph node metastases increased post-treatment. The patient subsequently started standard of care pembrolizumab treatment at 2 mg/kg intravenously every 3 weeks for 6 cycles. During hospitalization, the general condition of the patient was good, with signs of fatigue only present at the first 2 days after each pembrolizumab infusion. The treatment failed to result in an anti-tumor response. The patient then received 2 cycles of initially used chemotherapy regimen Pem-Cis. Interestingly, we detected a significant shrinkage in the enlarged mediastinal and hilar lymph node metastases, with the primary site in the left lung exhibiting no further progression.
Recent studies have suggested that clinical responses are associated with several potential biomarkers, including PD-1, PD-L1, and CD3.[ To investigate the clinical association of these factors with the efficacy of PD-1 blockade, we performed immunohistochemistry analysis of PD-1, PD-L1, and CD3 in specimens obtained from this patient. The results showed that the tumors from exhibited CD3+ T cell infiltration, but no PD-1 or PD-L1 expression (Fig. ).
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pmc-6310542-1
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A 45-year-old man, who lived alone, alerted the emergency service and reported violent chest and abdominal pains and vomiting. On the arrival of the paramedics, about 20 minutes later, the man was found in a state of cardio-circulatory arrest and death was ascertained. The body was surrounded by copious traces of vomit and hematic material, which also soaked the man's clothing. From circumstantial data gathered during an interview with the victim's family members, it emerged that the man had been complaining of general malaise and thoraco-abdominal pain for about a week. Anamnesis revealed a history of alcoholism, arterial hypertension, and an ischemic stroke 5 years earlier. Autopsy was performed 2 days after the death. On external examination, the body presented coffee-colored material in the perioral region, on the hands and on the clothes; no traumatic lesions were observed. On internal examination, the heart weighed 305 g and presented slight myocardial sclerosis and patent, elastic coronary arteries. About 300 cm3 of coffee-colored material was found in the left pleural cavity, and 350 cm3 in the right cavity (Fig. A). Moreover, a hemorrhagic infiltration of the esophageal wall was noted. On the right lateral wall of the distal tract of the esophagus, about 4 cm from the stomach, a vertical transmural tear of 3 cm in length was observed (Fig. B). The jejunal loops were filled with digested blood and semisolid material (Fig. C); the liver weighed 2385 g and presented marked steatosis (Fig. D). Histopathlogical examination was subsequently carried out on organ samples taken during autopsy and stained with hematoxylin and eosin. Microscopic examination revealed the presence of a mainly granulocytic inflammatory infiltrate of the esophageal mucosa and submucosa (Fig. A, B), with collections of undigested alimentary material and accumulations of hemosiderin highlighted by means of Perl stain (Fig. C, D). Toxicological examinations were performed on blood and urine samples taken during autopsy, but did not reveal the presence of alcohol or substances of abuse. The findings that emerged from the autopsy and the subsequent histopathological analyses enabled the cause of death to be attributed to acute cardiorespiratory failure due to pleural effusion secondary to esophageal rupture.
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pmc-6310582-1
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A 55-year-old woman with a medical history of CD, diagnosed in 1994 and surgically treated in 1995, was referred to our hospital for Crohn recurrence. Imaging and colonoscopy revealed a stenotic area in the neoterminal ileum, that was surgically treated. At 5 cm of preterminal ileum with stenosis and the anastomotic ileocolic block was removed. The post-surgical period was uneventfully. Histopathological examination showed an active Crohn small intestine with ulcerative and fissuring lesions associated with prominent fibrotic tissue proliferation, impinging on the muscolaris propria and also affecting the subserosal adipose tissue. Moreover, the stenosis was mainly sustained by mass-forming, prominent ganglioneuromatous hyperplasia at the submucosa and muscolaris layer, associated with marked follicular hyperplasia (Fig. D). The muscolaris mucosae was destroyed or showed marked hyperplasia and delamination and fusion with the muscolaris propria, resulting in obliteration of the submucosa. To better define the ENS morphological alterations, immunostaining was carried out with specific neurogangliar antibodies on different areas of small intestine and in non-involved wall of colon cancer specimens used as control. Following the study by Chen[ and Tertychnyi[, we immunostained for PD-L1 and SSTR2A to investigate its specific features in CD. Complete results and specific locations are listed in Table . Normally in non-inflamed gut and control cases, few nerve fibers are seen in the muscolaris mucosa, with very rare fine nerve twigs extending up into the lamina propria running parallel to the crypts (Fig. A), with a frequency of 1 every 3 to 4 crypts. Anti-synaptophysin and neurofilament antibodies highlighted large amounts of small, arborizing nerve fibers in the mucosa (Fig. B–C) and in bundles of nerve twigs lying in the delaminated muscolaris mucosae of our patient. In addition, in the mucosa we found a new-formed fibrillary network originating from the hypertrophic submucosal and myenteric plexuses, extending into the inflammation area at the subepithelial luminal mucosa site,[ and immunostained by PD-L1 and SSTR2A antibodies (Fig. ). Only described on GIST-1 (Dog-1) showed a focal positivity in the myenteric and submucosal plexuses but not in the hyperplastic neuromatous lesion and ganglion cells. On the contrary, anti-PD-L1 antibody weakly stained normal tissue plexuses but heavily stained the hyperplastic lesion and its bundles intermingled with muscolaris mucosae (Fig. ) and twigs, scattered among inflammatory cells, in the mucosa. Moreover, in our material SSTR2A was identified both in T-lymphocytes and in a nerve network in the mucosa under the luminal epithelium (Fig. ). This antibody reaction, negative in the control cases, can help to discriminate IBD from other causes of colonic inflammation, facilitating the identification of neural twigs in the mucosa of CD patients and predictive of neuromatous hyperplastic lesions deep in the wall. After surgery the patient was semestrally followed: the clinical and endoscopic evaluation was normal.
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pmc-6310935-1
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The female patient was 26 years old at the time of PGD-SR. Karyotype was 46,XX. Basal FSH, LH on day 3 and AMH value were respectively 8.0 IU/l, 6.5 IU/l and 6.3 ng/ml. She had a 30 days ovarian cycle. Uterine cavity and fallopian tubes resulted regular from diagnostic examination. The ovaries had a polycystic ovarian aspect. The patient had no previous pregnancy.
The male patient was 30 years old at the time of PGD-SR. After QFQ-banding karyotype analysis, he was found to have a karyotype with balanced translocation involving X chromosome and autosome 3: 46,Y,t(X;3)(p11.2;p14)mat (Fig. ).
The X-3 reciprocal translocation was transmitted from the mother that had the karyotype 46,X,t(X;3)(p11.2;p14) in the blood cells. In the family of male patient, the first sibling had a 46,XX normal karyotype (II-1). The third of three siblings (II-5) showed the same karyotype 46,Y,t(X;3)(p11.2;p14)mat of the patient. The parents of the patient were not consanguineous (Fig. ). His mother and siblings had a normal phenotype.
The male patient had a normal phenotype with normal genital tract.
Semen was characterized by severe oligoasthenoteratozoospermia (Semen concentration: 20.000 sperm /ml; 5% sperm with progressive motility, 2% of normal sperm). From blood cells analysis, the male patient resulted negative for microdeletions of AZFa, AZFb and AZFc regions []. The male endocrine was normal for FSH, LH, total Testosterone, Free Testosterone, 17bE2, Prolactin, HCG, aFP. The couple consulted for the first time an infertility center for primary infertility and asked to know 'the state of health' of the embryos as allowed by the Italian law on Medically Assisted Procreation [].
The following protocols of ovarian stimulation, oocyte and embryo vitrification, ICSI and embryos culture, embryo biopsy and NGS have been described elsewhere and are resumed as follow []. Each part of the protocol has been approved by the Institutional Review Board Unità di Medicina della Riproduzione - Centro HERA. The patients signed informed consent forms on all procedures prior application.
The female patient underwent two cycles of ovarian stimulation. In the first cycle, the metaphase II oocytes were vitrified. In the second cycle the metaphase II oocytes were used as fresh together with the previously vitrified/warmed oocytes.
The first ovarian stimulation was performed by the administration of recombinant FSH and LH (Puregon, MSD, Franklin Lakes, USA and Luveris: Merck-Serono, London, UK) from cycle day 2 in a luteal gonadotrophin-releasing hormone antagonist flexible schema (Orgalutran : MDS). Initial doses were 200 IU/day for FSH and 75 IU/day for LH. Luteal gonadotrophin-releasing hormone antagonist was given when the leader follicle reached 14 mm in diameter with a dosage of 0.25 mg/day. The second ovarian stimulation started on day 2 of the following cycle.
One ICSI session was performed using the accumulated vitrified/warmed oocytes together with the lately produced fresh oocytes and fresh male patient semen.
Vaginal ultrasound-guided aspiration of oocyte−cumulus complex (OPU) was performed 35 hours after human chorionic gonadotrophin administration (HCG 10,000 IU, Gonasi: AMSA, Rome, Italy). ICSI was performed on fresh oocytes 3h after OPU and on cryopreserved oocytes 1 hour after warming and in vitro culture with the same patient's fresh ejaculated spermatozoa sample.
After ICSI, in vitro culture was carried out in Continuous single culture complete medium with human serum albumin (Irvine Scientific, Santa Ana, USA) under mineral oil and in automated incubators with 5% CO2, 5% O2 at 37°C, fitted with time-lapse imaging acquisition (Embryoscope, Unisense, Aarhus, Denmark).
Embryo biopsies were performed on day 5 on expanded or hatching blastocysts. Few trophectoderm cells [5 to 10] were removed from a zona pellucida hole using a 1.48 um diode laser (OCTAX, Bruckberg, Germany) and a 20 um inner diameter biopsy pipette. After the biopsy procedure, each embryo was incubated until embryo vitrification and before blastocyst re-expension. The biopsied trophectoderm cells were washed in sterile phosphate buffered saline (PBS) solution and transferred into a 0.2 ml Eppendorf tube containing 4 ul of sterile PBS solution.
The vitrification and warming protocols for oocyte [] and embryos [] were previously described.
The biopsied trophectoderm cells were submitted to alkaline lyses and whole genome amplification according to Repli-g Single Cell protocol (Qiagen, Hilden, Germany). After quantification of amplified DNA, libraries were prepared from 100 ng of each sample and barcoded with IonXpressPlus Fragment and IonXpress Barcode Adapter kits (Life Technologies-Thermo Fisher (Carlsbad, USA). After quantification of the libraries, normalization to 100 pM and mix-up to obtain a final concentration of 8 pM, the eleven enriched libraries were loaded on Chip 16 V2. DNA sequencing was performed on ION PGM HiQ View Sequencing in Ion Personal Genome Machine. The updated Torrent Suite Software was used for base calling and mapping on human genome reference sequence Hg19. For each chromosome read coverage was corrected by guanine-cytosine calculation. Aneuploidy was diagnosed comparing data to baseline values multiple male samples. In all the process, a positive control with normal male DNA and a negative control from biopsy culture media were processed together with the samples to diagnose. Genetic analysis was validated when median absolute pair wise difference (MAPD) was inferior to 0.3. Chromosomal segments as short as 7 Mb could be detected. The protocol was previously validated on single cells from amniocytes with different karyotypes [].
Warming and single embryo transfer was performed on natural cycle at 7 days after LH surge.
The results of oocyte vitrification, ICSI, embryo culture and embryo biopsy analysis from vitrified/warmed and fresh oocytes are presented in Table .
The patient produced 8 metaphase II oocytes that were vitrified during the first ovarian cycles and 16 metaphase II oocytes in the second ovarian cycle that were used as fresh. Seven of the 8 vitrified oocytes survived to warming and were micro-injected together with the 16 fresh oocytes with the male patient’ semen sample and in the same ICSI procedure. The fertilization rates were 71.4% for vitrified/warmed oocytes (5 zygotes/7 micro-injected oocytes) and 75.0% for fresh oocytes (12 zygotes/16 micro-injected oocytes). On day V, 3 expanded or hatching blastocysts from vitrified/warmed oocytes (3 blastocysts/5 zygotes, 60.0%) and 8 expanded or hatching blastocysts from fresh oocytes (8 blastocysts/12 zygotes, 67.0%) were biopsied and vitrified.
The genetic analysis were validated and completed respectively in 100% of the biopsied blastocysts from vitrified/warmed and fresh oocytes. Chromosome contents of each blastocyst after PGD-SR are reported in Table .
According to the karyograms generated by IGV (Integrative Genomics Viewer), it was found that two embryos were diagnosed 46,XY, two embryos were diagnosed 46,XX; four embryos were diagnosed with unbalanced translocations and showed the trisomy 3p14→cen→3qter and monosomy Xp11.2→cen→Xqter, from 2:2 segregation and adjacent-2 disjunction. Three embryos were diagnosed aneuploid (45,X0 ; 45,XY,del [2] ;46,XY,del [8](qter →q22.1). Even if balanced translocation could be detected by NGS analysis, the 2 embryos diagnosed as 46,XX were known to have the balanced translocation inherited by the father and their true karyotype was: 46,X,t(X;3)(Xqter→Xp11.2::3p14→3pter;3qter➔3p14::Xp11.2➔Xpter)pat. On the same way, the 2 embryos diagnosed as 46,XY had a normal karyotype. Karyograms are shown in Fig. .
Prior to PGT-SR, a genetic counselling was performed and the couple was informed on the possible karyotypes due to father reciprocal translocation: embryo(s) with normal 46,XY, female(s) with balanced translocation and unpredictable phenotype, embryo(s) with unpredictable complete or partial aneuploidies.
After PGT-SR, the patients were informed on the result of the present PGD-SR. It was explained that among the viable embryos, the 2 male embryos had the true kayotype 46,XY, 2 female embryos had the reciprocal translocation 46,X,t(X;3)(Xqter→Xp11.2::3p14→3pter;3qter➔3p14::Xp11.2➔Xpter)pat.
Regarding the 2 female embryos with balanced translocation, it was explained that the phenotype should be normal, due to the preferable silencing of normal X as it seems to have happened in the patient’s mother. Consequently, deciding not to transfer balanced translocated female means taking the risk of eliminating from transfer and pregnancy a viable embryo with a normal phenotype.
On the other side, genetic disorders with different degree of gravity (from gonadal digenesis and premature ovarian failure to major genetic disorders and mental retardation) were reported in female patients with balanced reciprocal X-autosome translocations. This risk exists and remains unpredictable. The probability of occurring cannot be calculated.
Finally, one embryo had 45,X0 karyotype. It was explained that Turner Syndrome has a large expressivity [] and a very high in uterus lethality within the first trimester of pregnancy [, ].
It was reminded that de novo balanced translocation could not be detected by the present protocol of NGS.
After counselling, the couple asked to have one 46,XY embryo thawed and transferred.
The embryo n. 13 obtained from fresh oocyte, was thawed and transferred. The β-HCG test performed 12 days after embryo transfer was positive. Two weeks later the clinical pregnancy was ascertained by scan of embryonic sac and one foetal heart beat was observed. Non invasive prenatal testing (NIPT) for all autosome and gonosome chromosomes was performed on the 15th week of pregnancy and confirmed PGD-SR result.
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pmc-6310943-1
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A 38-year-old Sinhalese man presented to Teaching Hospital Kurunegala in Sri Lanka complaining of a 3-week history of fever, lethargy, and fatigability. He had not had any significant clinical conditions prior to this. He did not have any food or drug allergies while he was on regular anti-worm and anti-filarial prophylaxis. On clinical examination, he was febrile (39.4 °C), pale, and found to have a pansystolic murmur over the apex of his heart. He had leukocytosis (12.4 mm3) with predominant neutrocytosis (81%). His hemoglobin was 11.2 g/dL, C-reactive protein (CRP) was 231 mg/l, and erythrocyte sedimentation rate (ESR) was 100 mm/first hour. Transthoracic two-dimensional echocardiography (echo) revealed grade II mitral regurgitation, myxomatous, prolapsed mitral valve with 7 × 13 mm vegetation over the posterior mitral valve. Three sets of blood cultures were obtained within 1 hour from three different venipuncture sites; intravenously administered ceftriaxone was started empirically.
The following day, the three blood cultures became positive and were subsequently identified as Staphylococcus aureus. Intravenously administered cloxacillin 3 g 6 hourly was initiated while ceftriaxone was omitted. The (72 hours following initial culture) clearance blood cultures revealed Staphylococcus aureus and repeated clearance cultures following 72 hours remained negative. From that day onwards, for duration of 42 days, intravenously administered cloxacillin therapy was determined while clinical response was monitored with quarter hourly temperature, transthoracic two-dimensional echo, white blood cell/differential counts (WBC/DC), CRP, and ESR (Table ). Further, he was on acetaminophen and chlorpheniramine malate as required.
Following day 24 of intravenously administered cloxacillin, our patient developed high spike fever (39.6 °C) and his full blood count showed: WBC 990/mm3 with 34% of neutrophils and 22% eosinophils. His hemoglobin concentration was 9.5 g/dL, platelet count (202 × 106/mm3), D-dimer (320 ng/mL fibrinogen equivalent units), and both prothrombin time (PT) and partial thromboplastin time (PTT) remained normal. His CRP was 78 mg/l, ESR was 95 mm/first hour, and he was otherwise comfortable, showing no signs of sepsis beside the high grade fever. His vital signs (blood pressure and pulse) were normal. Repeat transthoracic two-dimensional echo was normal thus no vegetations were detected. Mild elevation of liver enzymes was observed and an ultrasound of his abdomen revealed no hepatomegaly: gamma-glutamyl transferase 192 IU/ml, alanine transaminase (ALT) 15 IU/ml, and alkaline phosphatase (ALP) 136 IU/ml. We omitted intravenously administered cloxacillin and kept him without antimicrobials while arranging a septic screening with a close observation of clinical parameters, WBC/DC, and inflammatory markers. His blood picture showed leukopenia with profound neutropenia and he had eosinophilia. Red blood cells and platelets were normal. He was clinically well and on day 6 after stopping cloxacillin, white blood cells (WBC) became normal with 44% neutrophils and 18% eosinophils. Liver function tests also returned to normal after cloxacillin discontinuation. He was treated with anti-pyretic as required. Subsequently, his septic screening became negative and transthoracic two-dimensional echo showed complete healing with no vegetations.
His serum was negative for filarial and Toxoplasma antibodies while stool was negative for oocytes and amoebic cysts. Further, his serum was negative for Epstein–Barr virus, cytomegalovirus, and hepatitis B antibodies. Subsequently his CRP and ESR became normal, and there was no further plan for cardiothoracic intervention or administration of antimicrobials. He was discharged from hospital and remained well 6 months later.
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pmc-6310945-1
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After 5 h of abdominal distention and pain, a 26-year-old Chinese woman reported hospital at 15:30 on December 3, 2017. The patient had previously been hospitalised for AP due to hyperlipidaemia on May 9, 2017, after which she had discontinued the lipid-lowering drugs prescribed by her doctor. During the 3 months before her admission in December, she resumed a high-fat diet. Approximately 7 h before disease onset, the patient consumed fatty food even after the occurrence of abdominal distention and pain. Her abdominal pain gradually worsened, and she vomited twice. The patient was diagnosed with AP based on her medical history, symptoms, signs, hemodlastase, and upper abdominal computed tomography (CT). After 10 h of hospitalisation, her abdominal pain became aggravated, leading to haemodynamic instability. Upper abdominal CT, liver, kidney, and heart function and electrolyte levels were reviewed. A comprehensive evaluation of the patient’s condition revealed a Ranson score of 4, Balthazar CT grade of D, APACHE II score of 17, and SOFA score of 9. The patient was diagnosed with SAP and multiple organ dysfunction syndrome (heart, liver and kidney). After hospital admission, the patient was treated with positive expansion, gastrointestinal decompression, and nutritional support, and continuous renal replacement therapy (CRRT) treatment was initiated on the second day. Based on an examination of abdominal imaging, intraperitoneal puncture and drainage was administered under the guidance of ultrasound on days 2, 4, 8, and 15. Subsequently, eight root drainage tubes were placed (pull out of the two tubes of the eight tubes on the 11th day) and jejunal nutrition was administered for 16 days after admission. By day 18 after admission, the patient’s renal function had restored, and intraperitoneal pressure had decreased from 32 mmHg at admission to 13 mmHg. The APACHE II and SOFA scores both became 3 on day 18. Onday 19, the patient’s temperature was within the healthy range at 06:00. The results of a routine blood examination were as follows: white blood cells (WBCs) 9.61 × 109/L, neutrophils 7.8 × 109/L (81%), C-reactive protein (CRP) 39.61 mg/L. Until 17:00 on day 19, the patient experienced chills and high fever. Her body temperature reached a high of 40.2 °C. After blood culture, linezolid and meropenem were performed to anti-infection treatment immediately. Routine blood examination, procalcitonin (PCT), and CRP levels were also observed (WBCs4.64 × 109/L, neutrophils 3.4 × 109/L [73.6%], CRP 51.15 mg/L, PCT 2.68 ng/mL). The patient continued to experience high fever on day 20. Thus, we administered a deep vein puncture tube and removed the remaining six root abdominal drainage tubes. All extracted peritoneal drainage tubes were used to make normalism the patient’s etiological cultivation. The causative agents were determined through high-throughput gene detection from a venous blood sample. Blood culture was performed again. These tests revealed that the patient had a fungal blood infection. Based on the conventional treatmet method, caspofungin was added to the drug regimen. On the 23rd day of treatment, Tc. glabrata was identified as the infecting agent through blood culture and gene detection.
Eventually, we discontinued the administration of meropenem and linezolid, but continued that of caspofungin. The patient’s body temperature was restored to within the normal range on the 25th day of treatment. During treatment, we monitored her routine blood panel and CRP levels once or twice daily. The results showed that her WBC count decreased gradually—to its lowest level on the 21st day of treatment (WBCs 0.58 × 109/L, neutrophils 0.1 × 109/L [2.20%]). Her haemoglobin and platelet levels also decreased. However, the duration of this decline was shorter than that of the WBC decline. The levels of other inflammatory markers also increased on the 23rd day of treatment (CRP 235.89 mg/L, PCT 10.85 ng/mL), alongside an increase in creatinine levels. On the 32nd day of treatment, the patient’s WBC count was finally restored to the normal range.
In summary, the patient’s temperature returned to normal with caspofungin treatment for 10 days. Blood culture was carried out on the 26th and 30th days after admission, and no bacterial growth was found in the two blood cultures. She was discharged on the 33rd day after treatment. And she was followed up every 10 days for 30 days after discharge. Results showed that her temperature was normal. Since then, she has been maintaining the low fat diet.
The timings of the observations (WBC counts, neutrophils, CRP, PCT, ect.) are shown in Fig. .
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pmc-6310953-1
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A 77-year-old male patient presents with severe non-radiating back pain at the thoracolumbar junction without accompanying sensorimotor deficits. Radiological assessment with conventional x-ray and magnetic resonance imaging (MRI) shows an osteolytic lesion with pathologic fracture of the T12 vertebra, unilaterally diminished vertebral body height and consecutive de novo scoliosis of 10° (Fig. ). The lesion also features a left paravertebral and epidural soft-tissue involvement without compromise of neurological structures. CT-guided transpedicular biopsy revealed multiple myeloma (Durie-Salmon stage I, R-ISS stage I). With a Spine Instability Neoplastic Score (SINS) of 13 points (junctional, non-mechanical pain, lytic lesion, deformity (scoliosis), < 50% collapse, unilateral involvement of the posterolateral elements), the lesion was judged unstable and surgical stabilization was planned prior to subsequent radiation therapy []. The patient underwent unnavigated dorsal instrumentation and fusion from T11 to L1 using CF/PEEK pedicle screws and rods (icotec AG BlackArmor® pedicle system 5.5 mm) with apposition of iliac crest autograft and demineralized bone matrix (Fig. ). Postoperatively, the patient had to wear a supportive customized thoracolumbar orthosis for 8 weeks. After rehabilitation and uneventful wound healing, a consolidating and analgesic radiation therapy with CT-based planning (total 30 Gray) was administered in a volumetric modulated arc therapy (VMAT) technique. A cytotoxic therapy with bortezomib, cyclophosphamide and dexamethasone has been initiated for systemic disease progression and achieved full remission after four cycles. No further surgical intervention was undertaken during the follow-up period (25 months). From a surgical point of view, the patient reported a very satisfactory outcome and stated an Oswestry Disability Index of 20%.
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pmc-6310953-2
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A 77-year-old male patient recognizes a mass in his dorsal upper arm. He seeks medical attendance when the lesion starts to be painful during the night a few weeks later. The patient also reports an unintended weight loss of 5 kg and recent night sweats. Radiological imaging shows an osteolytic lesion of the distal humerus with permeative growth and radial cortical penetration (Mirels’ score 8 points []) (Fig. ). Histopathologic evaluation after CT-guided core needle biopsy yielded an extensively necrotic metastasis from a prostatic carcinoma (pT1c cN0 M1b, Gleason Score 4 + 4 = 8, prostate-specific antigen 499 ng/ml). A systemic therapy with denosumab and goserelin was initiated. Due to significant cortical weakening (30%) with a non-displaced pathologic fracture, surgical stabilization was opted for prior to cytotoxic therapy with docetaxel and radiotherapy. Intralesional curettage was followed by open bridge plating using a CF/PEEK 4.5-mm locking compression plate (CarboFix Orthopedics Ltd. “Piccolo” Narrow Diaphyseal Plate) (Fig. ). The intraoperative handling of the chosen implant was straightforward and without unexpected incidents. Postoperatively, no weight-bearing and only careful passive mobilization was permitted for 6 weeks. Additionally, an arm sling was worn until complete wound healing had been attained. During routine follow-up, the patient presented without pain at his upper arm. The palliative radiotherapy (total 30 Gray) was administered subsequently. Likewise, the remaining follow-up (6 months) was uneventful. With regard to his arm, the patient reported very favourable and pain-free course allowing for any desired sports activity and stating a QuickDASH score of 22.5 points as well as a subjective limb value of 90%.
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pmc-6310953-3
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A 17-year-old male patient experiences intermittent pain and swelling at his left anterior tibia. Four months after onset of symptoms, the patient seeks medical advice. With a radiographically lytic and lobulated lesion of the tibial diaphysis featuring cortical erosion and focal penetration (Fig. ), referral to our institution was prompted. CT-guided needle biopsy revealed the rare finding of an intraosseous schwannoma. Even though benign, tumour resection was aspired in this symptomatic patient. To allow for better radiological surveillance during follow-up of this rare lesion, a CF/PEEK rather than a metallic implant was chosen. Due to the expansive growth (Mirels’ score 9 points []), prophylactic plate stabilization was needed. After complete curettage of the intraosseous lesion, the cavity was filled with cancellous bone allograft. Surgery was then completed by open bridge plating with use of a CF/PEEK 4.5-mm locking compression plate (CarboFix Orthopedics Ltd. “Piccolo” Narrow Diaphyseal Plate) (Fig. ). Again, the applicability of the chosen CF/PEEK implant was uncomplicated. Besides a prolonged wound secretion without need for special measures, the postoperative course was uneventful. After completing 48 h of relaxed bed rest, the patient was mobilized on crutches with partial weight-bearing (15 kg). During routine follow-up, the patient presented pain free with unremarkable clinical findings. Radiographically, progressive ossification could be detected throughout the follow-up (8 months). At the last follow-up, the patient-reported outcome using the SGOT (Swiss Society of Orthopaedics and Traumatology) Minimal Dataset revealed a pain-free well-being with full work capacity, a moderate limitation in sports activity (5/10 points) and a subjective limb value of 90%.
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pmc-6310982-1
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A 36-year-old Caucasian woman was evaluated with chief complaint of gluteal pain radiating to her leg. Her medical history was remarkable with gunshot injury to the affected leg with multiple pellets dispersed into her pelvis and proximal part of the thigh, as shown in Figs. and . She had gunshot injury 20 years ago. She was previously diagnosed as having lumbar disc herniation at L4–5 level. She underwent a previous discectomy outside our institution 2 years ago. A radiological examination revealed the presence of recurrent disc herniation, as well as multiple shotgun bullets in her pelvis and thigh. One of those bullets was deep into the sciatic nerve inside her quadratus femoris muscle.
Electromyography (EMG) showed the presence of chronic sciatic nerve injury. Since it was clinically impossible to distinguish lumbar disc herniation from the sciatic injury, we decided to proceed with removal of the foreign object and neurolysis of the sciatic nerve followed by L4–5 discectomy and fusion. We decided to perform those procedures in two different settings. The first surgery included access to the sciatic nerve in the upper portion of her thigh and exposing the nerve fibrotic bands around the nerve. The dissection proceeded deep into the nerve within a muscle, where a bullet was found and removed. The distance from the bullets to the nerve was approximately 2 cm. Muscle tissue around the bullets was excised for analysis. For comparison, another specimen was obtained from the gluteal muscle, superficially away from the nerve and all the bullets. Two weeks later, she underwent scheduled L4–5 discectomy and fusion. Her postoperative course was uneventful. On follow-up examination at 6 months, she was essentially symptom free.
A scanning acoustic microscope (AMS-50SI) developed by Honda Electronics (Toyohashi, Japan), whose schematic setup is shown in Fig. , was used in AI mode. It has a transducer with quartz lens, a pulser/receiver, an oscilloscope, a computer, and a display monitor. An 80 MHz transducer is installed within the microscope, which generates the signals and collects the reflected acoustic waves. Water is the coupling medium between the quartz lens and the substrate. For two-dimensional scans, an X-Y stage, controlled by a computer, is used. An oscilloscope analyzes the reflected signals from both the reference and target material after being collected by the transducer. As a result, acoustic intensity and impedance maps of the region of interest with 300 × 300 sampling points are obtained.
The principle of SAM in AI mode is demonstrated in Fig. . Distilled water is widely used as reference. The signal reflected from the target is
where, S0 is the generated signal by the 80 MHz transducer, Ztarget is tissue’s AI and Zsub is the polystyrene substrate’s AI (2.37 MRayl). The tissue’s AI is calculated by combining the reflected signals from the tissue and the reference. The signal reflected from the reference iswhere Zref is the AI of water (1.50 MRayl). Then, the target’s AI is written aswith a constant signal S0 [] generated by the transducer.
Electron microscopy-based imaging and chemical analysis studies were performed in a JEOL JIB-4601 focused ion beam scanning electron microscope (FIB-SEM) multi-beam platform coupled with an Oxford X-MaxN EDS system, as shown in Fig. .
Blood samples were collected in test tubes containing ethylenediamine-tetraacetic acid (EDTA) and no anticoagulant on the day of the first surgery (foreign object removal) prior to the procedure. Then, 2 ml of 20% trichloroacetic acid (TCA) was supplemented into the blood samples to release the red blood cells (RBC) and other ingredients. The supernatant part was received from blood with TCA by centrifugation at 4000 revolutions per minute (rpm) for 20 minutes for the analysis of Pb and cadmium (Cd) within total blood. Coagulation of blood samples enabled serum trace element analysis: chromium (Cr), Fe, Cu, magnesium (Mg), manganese (Mn), selenium (Se), and Zn. The serum specimen was prepared using Hettich Universal centrifuge by centrifugation at 3000 rpm for 15 minutes, separating from cells immediately after and storing at − 20 °C until the analysis [].
After weighing the left sciatic nerve tissue samples, they were digested with 2 ml of 65% nitric acid (HNO3) at 180 °C in the incubator for 1 hour. Then, 2 ml of 65% perchloric acid (HClO4) was added into the cooled mixture. Then, the mixture was digested at 200 °C in the incubator until the volume was halved. Digested materials were vortexed and diluted in water to a total volume of 10 ml. Concentrations were given in micrograms per gram (μg/g) wet tissue weight [].
All glassware were maintained at 10% (volume/volume; v/v) HNO3 before use, cleaned with deionized water, and dried in an incubator at 100 °C overnight. Pb, Cd, Cu, Cr, Fe, Mn, Se, and Zn elements were detected by inductively coupled plasma optical emission spectrophotometer (ICP-OES 6000, Thermo, Cambridge, United Kingdom). Measurements for each element were done three times and averaged. The ICP-OES was operated with argon carrier flow rate of 0.5 L/minute, plasma gas flow rate of 15 L/minute, sample flow and elusion rate of 1.51 L/minute, and peristaltic pump speed of 100 rpm, selecting the suitable wavelength for Pb, Cd, Cr, Cu, Fe, Mn, Se, and Zn, which were 220.353 nm, 228.802 nm, 267.716 nm, 324.75 nm, 285.213 nm, 357.610 nm, 196.090 nm, and 206.200 nm, respectively. Transport lines were obtained using 1.25 mm internal diameter polytetrafluoroethylene tubing. Element levels were indicated in micrograms per deciliter for serum (μg/dl) and μg/g for wet tissue. The standard concentrations for standard graph calibration were arranged from standard stock solutions of 1000 μg/ml for each analyzed element [].
The tissue samples were investigated by using AI mode of SAM. Figure shows the AI map of the tissue obtained away from the gunshot. The map was constructed by collecting the reflections of acoustic signals, generated by the transducer within SAM, from surfaces of the reference (water) and the tissue sample on the polystyrene substrate. At specific locations within the sample, the AI was calculated to be higher than 2 MRayl, indicating accumulation of elements with different elastic properties. Figure shows the AI map of the tissue obtained close to the gunshot. As can be seen in this image, almost everywhere had an AI of greater than 2 MRayl.
SEM images of the tissue far away from the gunshot were obtained at magnifications of 5000 × and 500 ×, as shown in Figs. and , respectively. Similarly, SEM images for the tissue close to the gunshot were obtained at magnifications of 5000 × and 500 ×, as shown in Figs. and , respectively. The images were acquired at 5 keV energy for both tissue samples.
The SEM images show that the tissue far away from the gunshot keeps its original structure, whereas the tissue close to the gunshot seems to be deformed and torn up. These results demonstrate the degree of damage the impact of gunshot causes on soft biological tissues.
Table represents the EDS measurements in SEM, carried out for determining the elemental distribution differences in the deformed tissues. The measurements show the percentages of the residue elements detected on tissues far away from the gunshot and close to the gunshot. According to the results, among all residue elements, Pb, Cr, Fe, and Mn are found to be higher in weight content in the region close to the gunshot, when compared to distant region. Cd and Cu levels do not differ much; however, Zn level is lower in the tissue close to the gunshot.
We determined Pb, Cr, Cd, Cu, Fe, Mn, Zn, and Se levels in both tissue samples. Pb, Cr, Fe, Se, and Mn levels were higher in the tissue close to the gunshot, conversely, Zn level was lower in this sample (Table ). Blood Pb and blood Cd, and serum Cr, Cu, Fe, Mn, Se, and Zn levels of our patient were also analyzed and the results are shown in Table , however, we did not observe significant differences when compared to reference values.
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pmc-6311039-1
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A previously healthy, fully immunized, 16-month-old girl was hospitalized for high grade fever (maximum axillary temperature of 39.8 °C), vomiting and refusal to feed of 4 days’ duration and irritability of recent onset. She had been receiving oral antibiotic treatment with amoxicillin-clavulanic acid (50 mg/kg/day every 8 h) for 24 h, without any clinical improvement. On admission (day 1) the patient was irritable but in good general condition. Physical findings were as follows: body weight 11 kg; heart rate 101 beats/min; body temperature 38 °C; oxygen saturation in room air 98%; blood pressure 90/50 mmHg. The cardiorespiratory and abdominal examinations were normal and no skin rash was observed. There was no sign of meningitis. Laboratory tests showed elevated white blood cell (WBC) counts of 14,090/mmc (75.7% neutrophils), while the C-reactive protein (CRP) concentration was 5.76 mg/dl (normal value < 0.5 mg/dl). Electrolytes, renal function and coagulation tests were within the normal range. Given her vomiting, the ongoing oral antibiotic treatment was stopped and intravenous ceftriaxone (100 mg/kg/day in a single dose) was started in the suspicion of a bacterial infection.
On day 2 the patient rapidly worsened. She was lethargic and preferred the lying position. Neck stiffness and Brudzinski’s sign were also noted. A computed tomography scan of the brain was normal, with no signs of increased intracranial pressure. A lumbar puncture was performed, revealing clear cerebrospinal fluid (CSF) containing 840 cells/mmc with neutrophilic predominance and glucose and protein concentrations of 38 and 44 mg/dl respectively. Empiric parenteral antibiotic treatment with ceftriaxone (100 mg/kg/day) was continued and intravenous antiviral therapy with acyclovir (30 mg/kg/day in 3 doses) was started. Gram-staining resulted negative.
On day 3, a real-time polymerase chain reaction (RT-PCR) for viruses and bacteria was positive for L. monocytogenes. Ceftriaxone was therefore discontinued and intravenous ampicillin (200 mg/kg/day in 4 doses) and gentamicin (5 mg/kg/day) were started.
On day 4, the CSF culture identified L. monocytogenes, while the blood culture was negative. A brain magnetic resonance imaging scan showed mild meningeal enhancement without any sign of parenchymal involvement.
The patient improved rapidly after the initiation of ampicillin and gentamicin. She was completely afebrile from day 7 and was progressively alert and communicative by day 10. Ampicillin and gentamicin were continued for a total of 21 days, while acyclovir was continued until the RT-PCR for Herpes simplex viruses proved negative. The patient was discharged after 22 days in good general condition and without any neurologic sequelae. Immunological screening, including an evaluation of cellular immunity (total and subpopulations of T cells), humoral immunity (immunoglobulin levels and subclass IgG) and complement (C3, C4, AP50, CH50), was normal. An HIV test was negative and there was no iron overload. A hearing test (auditory evoked potentials) was normal. At a follow-up visit after 1 month, her clinical presentation was normal and there were no signs of the disease. No source of infection was clarified in her recent history.
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pmc-6311045-1
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A 10-year-old girl first noted a swollen left knee and underwent repeated arthrocentesis. At age 13, she underwent arthroscopic surgery and was diagnosed with benign TGCT. She subsequently underwent numerous synovectomies to treat local recurrences and radiation therapy to her left knee joint at age 15. Ultimately, her disease spread to her upper calf and posterior thigh. At age 32, her upper calf lesion was resected, and the tumor in her posterior thigh was treated with radiation. At age 34, swelling of an inguinal lymph node was noted and fine needle aspiration was consistent with malignant TGCT. Other staging scans revealed a pelvic mass and a sub-centimeter pulmonary nodule. Her disease remained stable after four cycles of doxorubicin/ifosfamide and she subsequently received gemcitabine/docetaxel as well as radiation therapy to her pelvis with stable disease for three months. She underwent left-sided above the knee amputation and excision of the intrapelvic masses. Eight months later, enlarging pulmonary nodules were resected. She was treated with sirolimus (rapamycin) and remained disease-free for eight months until a pulmonary nodule and two inguinal masses were noted. In 2007, at age 37, she was referred to our hospital and treated with sorafenib for four months with mixed response. She subsequently began on sunitinib 37.5 mg daily. Interval restaging scans showed no evidence of progressive disease for 15 months. She had significant interval progression of a right-sided pelvic mass while she temporarily stopped sunitinib in the perioperative setting of resection of painful metastatic nodules near the amputation stump (Fig. a, b, and c). Given that the drug had a significant role of controlling the disease, her sunitinib was restarted in combination with sirolimus (rapamycin). Her disease was under good control for eight additional months until she had progressive disease in the pelvis and underwent hemipelvectomy. She died of the disease at age of 39, six years after the malignant transformation.
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pmc-6311045-2
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A 53-year-old man was diagnosed with malignant TGCT after undergoing resection of a soft tissue tumor in the right proximal rectus femoris muscle. He underwent adjuvant radiation therapy but developed a local recurrence and underwent another wide resection five months after the initial wide resection. One year after the initial wide resection, he developed further progression of his tumor in the thigh and repeat staging evaluation revealed involvement of a right inguinal lymph node and bilateral small pulmonary nodules (Fig. d, and e). He was enrolled in a clinical study with sorafenib (NCT00330421); however, he was taken off study after a month because of dramatic disease progression in the lungs (Fig. f) as well as in the thigh. The patient died of disease 20 months after diagnosis.
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pmc-6311045-3
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A 55-year old woman presented with an enlarging mass in the posterior aspect of her right knee. The initial MRI revealed an extensive soft tissue lesion in the calf with fluid levels present (Fig. g, and h). Biopsy was consistent with a benign diffuse-type TGCT. Three months after she underwent resection of the mass in the posterior popliteal fossa, she developed a local recurrence (Fig. i). Above-knee amputation followed the second resection of the recurrent tumor whose pathology revealed malignant transformation. CT scans two months later revealed metastases to the right inguinal nodes and the lung (Fig. j, and k). She subsequently began imatinib, but treatment was terminated because of progressive disease. Four cycles of doxorubicin/ifosfamide demonstrated partial response, resulting in disappearance of pulmonary nodules and significant decrease in size of inguinal nodules (Fig. l). She was enrolled in two clinical trials of investigational mTOR inhibitor or placebo and of an investigational PI3K/mTOR inhibitor, neither of which provided significant clinical benefit by the time of first follow-up CT. She then completed two cycles of liposomal doxorubicin, with no clinical benefit. She was subsequently treated with two cycles of ifosfamide and palliative radiation to her leg, resulting in marked response of the tumor in the thigh, but progressive disease systemically. Her disease then showed partial response to gemcitabine/docetaxel for five months before developing progressive disease in the lungs. She died of the disease 23 months after the diagnosis of malignant TGCT.
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pmc-6311045-4
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A 46-year-old woman presented with a 10-cm mass involving the right psoas muscle, the gluteal muscles, and the iliac bone. A CT scan at presentation demonstrated sub-centimeter pulmonary nodules, in addition to the pelvic mass. The CT-guided biopsy was consistent with malignant TGCT. Cytogenetic studies demonstrated an unbalanced t (1;2) translocation. Because of severe pain in her right hip, she underwent palliative radiation therapy (54 Gy) to her right pelvis, which dramatically improved her intractable pain. Her disease remained stable after four cycles of doxorubicin/ifosfamide. She enrolled in a clinical trial of nilotinib for TGCT (NCT01207492) but progressed after 1 month. She was then treated with gemcitabine/docetaxel without clinical benefit, and she died of the disease nine months after diagnosis.
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pmc-6311045-5
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A 44-year-old man first noted a mass in the vastus medialis. A biopsy demonstrated a diagnosis of benign diffuse-type TGCT (Fig. p). The patient elected to follow a course of observation. Three years later, he noted an increase in the size of the mass and subsequently underwent a marginal excision of the tumor. Pathology was consistent with malignant TGCT with positive margins (Fig. q). Staging CT revealed multiple pulmonary metastases. The patient subsequently participated in a blinded clinical trial of doxorubicin with an investigational drug or placebo and developed a partial response; he completed 6 cycles before electing to stop chemotherapy. He later developed metastatic disease to the subcutaneous tissue, pleura, liver, mesentery, bones, and sacral nerve roots and was treated with palliative radiation to the spine with concurrent paclitaxel, which failed to control his disease. Subsequent gemcitabine/vinorelbine provided no clinical benefit, and he died of disease 17 months after diagnosis of malignant TGCT.
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pmc-6311045-6
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A 54-year-old man noted progressive discomfort and swelling in his left knee. Resection of the lesion revealed benign diffuse-type TGCT. Despite resection, he developed rapid recurrence within weeks. Given the aggressive nature of the recurrent tumor, the patient was treated with two cycles of doxorubicin/ifosfamide in a neoadjuvant setting that was stopped for progression of disease, and he then underwent above-knee amputation. Pathology confirmed multifocal malignant transformation of TGCT. One year after amputation, he developed painless inguinal lymphadenopathy from metastatic TGCT. Six months later he developed malaise, dyspnea on exertion, nonproductive cough, and night sweats. Chest CT demonstrated a left sided pleural mass which was confirmed as metastatic malignant TGCT by biopsy. PET-CT revealed several pulmonary nodules, a focal hypermetabolic lesion in the L3 vertebral body, and a rapidly progressing pleural lesion. Systemic treatment with imatinib showed mixed response, with resolution of FDG avidity of the bulk of the mass but development a new hypermetabolic component invading his chest wall. He received palliative radiation to this mass and then initiated pazopanib but within one week developed symptomatic progression and entered hospice care. He died 3 years after initial diagnosis, 2 years after diagnosis of malignant TGCT, and 13 months after he developed metastatic disease.
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pmc-6311067-1
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A 53-year-old male was transferred from Peripheral Hospital Hatharaliyadda (PHH) to Teaching Hospital, Kandy (THK) in a state of circulatory failure for specialized care. He was a previously well ‘tree cutter’ working close to his residence situated in a hilly terrain in the Northern slope of central hills of Sri Lanka where rich lust green vegetations and tropical trees are in abundance. His routine was to cut trees in the tea estates in the area and to carry the logs to the closest motorable road.
He developed fever with myalgia and headache 5 days prior to the admission to PHH. On the 4th day of fever he had noticed a rash over his body. As his condition deteriorated on the 6th day of the illness, he was transferred to THK. On admission, he was febrile and recorded temperature was 102 °F. He had a generalized discrete erythematous macular rash in most areas of the body including palms and soles. Also he had swelling of both ankle joints. He denied any tick bite prior to illness. There was no eschar found. He had neither lymphadenopathy nor splenomegaly. But the liver was palpable 2 cm below costal margin. Lungs were clear to auscultation. (Fig. ) He had a thready pulse of 100/min with a blood pressure of 80/50 mmHg.
He was initially resuscitated with intravenous normal saline and managed as septic shock. The presence of skin rash prompted to consider a spotted fever rickettsial infection. Therefore, he was started on intravenous ceftriaxone and oral doxycycline. Since his blood pressure did not improve with fluid resuscitation a central line was placed and intravenous norepinephrine infusion at a rate of 0.4μg/kg/min was commenced along with septic dose of intravenous hydrocortisone 50 mg/6hourly. His plasma random glucose was normal. Initial electrocardiogram did not show ST/T wave abnormalities and Chest radiograph was normal. His serial investigations during the hospital stay are shown in Table .
With inotropic support, antibiotics and maintenance fluids he remained stable for the next 36 h. His blood cultures, urine cultures and retroviral studies were negative. During the latter part of the second day of admission to THK he developed progressively worsening shortness of breath with hypoxemia and hypotension. Blood gas analysis showed type 1 respiratory failure with pO2/FiO2 ratio of 135.8. Repeat chest radiograph showed bilateral alveolar and interstitial shadowing of both upper and mid zones. ECG revealed sinus tachycardia with no significant ST/T wave changes. 2D Echo cardiogram showed a ventricular ejection fraction of 40–45% with global hypokinesia of myocardium suggestive of myocarditis. Troponin-I titre was positive at 4.9 ng/ml (Normal < 0.12 ng/ml) and NTproBNP (N-terminal pro b-type natriuretic peptide) value was elevated at 11954 pg/ml. At this juncture, elective intubation was done and the patient was transferred to the Intensive Care Unit for assisted ventilation. (Fig. ).
The management team identified some issues with regard to diagnosis and choosing the appropriate treatment for the patient. Echocardiographic findings, elevated troponin titre and elevated BNP were consistent with myocarditis leading to heart failure causing pulmonary oedema and hypoxemia. The possibility of ARDS was considered based on clinical, blood gas and radiological evidence. Spotted fever was considered to be the most likely diagnosis because of the presence of the typical rash. Other differential diagnoses included leptospirosis with myocarditis and pneumonitis. But the rash and lack of liver and renal involvement was not in favor of leptospirosis. Streptococcal and Staphylococcal toxic shock syndromes and meningococcal sepsis were also taken into consideration, but inability to fulfill diagnostic criteria and persistently negative cultures were against them. Hemophagocytic lymphohistiocytosis (HLH) is also known to complicate many zoonoses including spotter fever infections [, ]. However, absence of cytopenias and the splenomegaly made it less likely and further screening tests for HLH were not performed.
Considering the poor response to previous antibiotics, intravenous chloramphenicol 500 mg 6 hourly was added to the treatment regimen as authors personally had seen good response particularly in patients with severe disease. He required 3 inotropes in increasing doses, including norepinephrine 0.5μg/kg/min, Dobutamine 10μg/kg/min and Dopamine 15μg/kg min, to maintain the blood pressure for the next 24 h. In view of myocarditis, IV hydrocortisone dose was increased to 200 mg/6hourly. Within 12 h from starting chloramphenicol and increasing the dose of steroids, his clinical parameters started to improve. By next day tailing off of the inotropic support was possible. On the 3rd day in the Intensive Care Unit, he was extubated and on the 4th day he was transferred back to the High Dependency Unit of the medical ward. The skin rash started to fade leaving few necrotic areas over the hands. All three antibiotics were stopped after the completion of 7 days. He did not develop any treatment related complications. He was recovered enough to be discharged from the hospital on the 10th day of admission.
In two weeks’ time, he was reviewed in the out-patient clinic and found to be completely asymptomatic. For the confirmation of diagnosis, 1st acute blood sample was tested for R. conorii indirect immunofluorescence antibodies (IFA) at the reference laboratory of University of Peradeniya which showed moderately high positive titre (1/256). Ten days later, 2nd blood sample was tested with IFA which showed rising titre (1/1024) confirming the diagnosis. Further species identification was not possible due to unavailability of facilities. Unfortunately patient did not turn up for the follow up echocardiogram.
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pmc-6311077-1
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A 78-year-old Caucasian male was diagnosed with temporal arteritis based on clinical presentation and biopsy of temporal artery showing granulomatous inflammation. The chest HRCT revealed pulmonary changes similar to autoimmune ILD. Based on radiological findings, the diagnosis of pulmonary TB was considered but sputum smears and microscopy of bronchial washings were negative and this diagnosis was rejected. Thus, the treatment with methylprednisolone (8 mg/daily) for temporal arteritis was initiated more than a half-a-year ago. At the time, patient was using amiodarone tablets 400 mg/daily for recurrent atrial fibrillation (AF) in 2002.
Patient arrived at the rheumatology outpatient department, complaining of fever and dyspnea, his parameters of central hemodynamics were normal, ECG showed sinus rhythm, C-reactive protein (CRP) was 118 mg/l. The diagnosis of bilateral pneumonia, consistent with pulmonary vasculitis, was established with chest X-ray, and patient was admitted to the rheumatology department. Empiric antibiotic therapy with cefuroxime (4.5 g/daily) and methylprednisolone (32 mg/daily) for suspected exacerbation of vasculitis were prescribed.
On the third day of hospitalization, patient complained of malaise, pressure and tightness in his chest. ECG was performed and the AF was identified. The patient was transferred to the Intensive Care Unit (ICU) for direct current cardioversion into the sinus rhythm. Later the patient was successfully transferred back to the rheumatology department. After 24 h, another episode of AF recurred. Electrolytes were within normal range. Pharmacological conversion was prescribed with 300 mg amiodarone IV solution. Despite the pharmacological management of the AF, patient presented with severe dyspnea, tachypnea with signs respiratory insufficiency. The multidisciplinary consult concluded that the patient suffers either from autoimmune interstitial lung disease or drug induced lung injury. In addition, there was little evidence to exclude bacterial infection. Thus, it was decided to discontinue amiodarone therapy, initiate corticosteroid therapy, and repeat bronchoscopy, take sputum smears and bronchial washings for bacterial diagnostics and chest HRCT. The chest HRCT identified pulmonary emphysema, thickening of intra- and interlobular septa, with random distribution nodules, ground-glass opacities, fibrosis and traction bronchiectasis, progression of mediastinal lymphadenopathy (Figs. a, a and a). Fiberoptic bronchoscopy with bronchial washings and brushings was performed. Acid fast bacilli (AFB) were found on Ziehl-Nielsen microscopy. The diagnosis of TB was confirmed and the anti-TB therapy was initiated with isoniazid (300 mg/day), rifampicine (600 mg/day), ethambutol (1200 mg/day) and pyrazinamide (2000 mg/day). Control chest HRCT was performed after four months of TB treatment. Signs described on earlier chest HRCT regressed – nodules became more restricted with thinning of intra- and interlobular septa shown (Figs. b, b and b). However, the patient developed pneumonia. Blood culture did not confirm bacterial growth, but sepsis was diagnosed clinically. Empiric antibiotic therapy was prescribed. Despite the treatment, multiple organ dysfunction syndrome evolved and patient died. The lung biopsy was not performed thus it is not possible to completely exclude amiodarone induced interstitial lung disease accompanying pulmonary TB.
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pmc-6311165-1
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A 65-year-old man presented with a subcarinal mass incidentally found during the preoperative work up for bladder cancer. Magnetic resonance imaging revealed a circumscribed mass suggesting a bronchogenic cyst (Fig. ). After completing a trans-urethral resection of bladder cancer, he was referred to our department and planned to undergo a surgical resection of the tumor.
The patient was placed in the prone position and his right arm was raised cranially. Under one-lung ventilation, the initial 5-mm port was inserted at the fifth intercostal space (ICS) on the right middle axillary line (port 1, Fig. ). CO2 was insufflated through this port at a pressure of 8 mmHg. Under a thoracoscopic view, the second 5-mm port and third 12-mm port were inserted at the ninth ICS on the scapular line (port 2) and seventh ICS on the middle axillary line (port 3), respectively. With the thoracoscope inserted through port 2, the surgeon held a grasper and electrocautery via port 3 and port 1.
In addition to CO2 insufflation, a gravity effect also facilitated the exposure of the posterior mediastinum and subcarinal mass wide enough without any retraction (Fig. a). The mediastinal pleura was incised inferiorly to mobilize the tumor from the pericardium and bronchus (Fig. b, c).
However, 10 min after beginning the surgery, he required bilateral ventilation because of hypoxemia when his O2 saturation dropped to 81% probably caused by diaphragmatic compression (his body mass index was 25.3). Nevertheless, the operative field was maintained excellently even with bilateral ventilation and we completed the total resection of the tumor successfully (Fig. d). The operative time and estimated blood loss were 126 min and 1 g, respectively. A histological examination revealed that the cyst wall lined by pseudostratified ciliated epithelium contained smooth muscle, consistent with a diagnosis of a bronchogenic cyst. The postoperative course was uneventful, and he was discharged 3 days after surgery.
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pmc-6311171-1
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An 80-year-old male with hypertension and chronic kidney disease was admitted to our hospital because of epigastric pain that had begun after dinner 1 day before admission. The patient reported no use of nonsteroidal anti-inflammatory drugs.
On examination, the patient’s temperature was 37.0 °C, heart rate was 101 beats per minute, blood pressure was 185/93 mmHg, respiratory rate was 18 breaths per minute, and oxygen saturation was 96% while the patient was breathing ambient air. The patient’s body mass index was 26.3 kg/m2. Mild epigastric tenderness was present. The remainder of the physical examination was normal. The laboratory data on admission were as follows: white blood count 9400/mm3, the C-reactive protein level 7.53 mg/dl, red blood count 419 × 104/mm3, hemoglobin 13.4 g/dl, platelets 16.8 × 104/mm3, total bilirubin 0.8 mg/dl, aspirate aminotransferase 21 IU/l, alanine aminotransferase 16 IU/l, alkaline phosphatase 232 IU/l, γ-glutamyl transferase 15 IU/l, amylase 86 IU/l, blood urea nitrogen 32 mg/dl, and creatinine 1.99 mg/dl, and estimated glomerular filtration rate is 26 ml per minute per 1.73 m2 of body surface area. Chest and abdominal radiography showed no abnormalities. Computed tomography (CT) of the abdomen showed a linear, hyperdense, foreign body that appeared to penetrate through the posterior wall of the gastric antrum (Fig. a). There was no evidence of free air, abscess formation, migration of the foreign body into the pancreas, or pancreatitis (Fig. b).
As the patient had a history of fish bone ingestion, we made a diagnosis of localized peritonitis caused by fish bone penetration of the posterior wall of the gastric antrum. We first attempted to remove the foreign body endoscopically, but failed because it was not detected. Hence, an emergency laparoscopic surgery was performed. The patient was placed in a supine position. The operator stood on the left side of the patient, the assistant on the right side, and the scopist between the patient’s legs. Four trocars were placed: one above the navel for the laparoscopy (12 mm), two in the upper left abdominal quadrant (5 mm), and one in the upper right abdominal quadrant (5 mm). Laparoscopic gastrectomy techniques were used to separate the greater omentum from the transverse colon and open the lesser sac. A linear, hard, foreign body was found in the adhesive tissue between the gastric antrum and the pancreatic body (Fig. a). The foreign body was safely removed from both the pancreas and stomach laparoscopically. The foreign body was identified as a 2.5-cm-long fish bone, (Fig. b). The length of the fish bone embedded in the pancreas was about 2 cm. There was a minor laceration at the site of the pancreatic injury. Neither fat saponification nor hematoma around the pancreas was identified. We did not perform suture repair or local debridement for the site of the pancreatic injury. Because the site of the penetrated gastric wall was small and a leak was not observed, we did not perform suture repair or cover the site of the penetrated gastric wall with the omentum. Intraperitoneal lavage was performed, and a drain was placed in the lesser sac.
Clear fluid was drained, and the postoperative serum amylase levels were normal. The patient recovered without complications and was discharged on the seventh postoperative day.
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pmc-6311172-1
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Abdominal computed tomography for regular monitoring of uterine fibrosis in a 49-year-old woman found a hypodense lesion 7 cm in diameter with a clear boundary near the gallbladder (Fig. a, b). No obvious change in size and internal density of uterine fibrosis had been observed during these 5 years (Fig. b). She had no previous history of alcohol or drug abuse. Ultrasound revealed a well-defined, non-calcified tumor between the gallbladder and liver (Fig. ). Magnetic resonance imaging demonstrated a hypointense tumor that compressed the gallbladder and liver on precontrast T1 mapping (Fig. a). T2-weighted images revealed hyperintense tumor with delayed enhancement on arterial phase and portal venous phase (Fig. b) followed by a delayed washout on the hepatocyte phase. Clinical evaluation and laboratory results were nonspecific, and serum tumor markers including carcinoembryonic antigen, cancer antigen (CA) 19-9, alpha-fetoprotein (AFP) and squamous cell carcinoma antigen were within their normal ranges. The findings were consistent with a gastrointestinal stromal tumor (GIST) or another benign tumor originating from the liver or gallbladder. Accordingly, we planned firstly laparoscopic partial hepatectomy concomitant with gallbladder resection. Lymphadenectomy among the hepatoduodenal ligament were also planned under the situations where malignant tumor was suspected intraoperatively. Under the laparoscopic view, a soft tumor had expansively progressed behind the gallbladder, with dorsal compression of the liver (Fig. ). The tumor was easily separated from Laennec’s capsule of the liver at the gallbladder neck and body without adhesion, which indicates the tumor is benign. Therefore, operative policy changed to tumor enucleation with cholecystectomy. Frozen sections including the surgical margin of the cystic duct were negative for tumor cells. As the tumor was moderately attached to the liver at the fundus of the gallbladder, the liver parenchyma was partially resected en bloc to ensure that the surgical margins were free of tumor tissue.
The resected specimen included soft and white tumor tissue with clear boundaries that was located between the liver and gallbladder (Fig. ). Pathological examination following Hematoxylin and Eosin and immunohistochemical staining of tumor specimens was consistent with SFT. The specimens included spindle-shaped tumor cells with elongated nuclei (Fig. a), present in both tangled and patterned arrangements in the subserosal layer of the gallbladder (Fig. b, c). The tumor tissue had a storiform pattern with alternating hypocellular and hypercellular areas with some showing myxoid degeneration. The tumor cells were positive for CD34, CD99 and B-cell lymphoma (BCL)-2 and negative for S100 and alpha smooth muscle antigen (αSMA) staining (Fig. d), and few cells were positive for the cell proliferation marker Ki-67/MIB-1. The tumor cells were negative for SMA, keratin, cytokeratin (AE1/AE3), CD117, epithelial membrane antigen, and desmin. The pathological diagnosis was SFT originating from the cystic plate.
The postoperative course was uneventful. She was discharged on postoperative day 9. Chemotherapy was not considered necessary, and postoperative follow up at 18 months found the patient well without any sign of recurrence. Periodical check-up for uterine fibrosis by gynecologist is also continued.
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pmc-6311175-1
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The patient was a 69-year-old man who was a known case of type 2 diabetes mellitus (T2DM). He initially presented with sigmoid colon cancer that progressed to obstructed necrotizing enteritis. He had undergone subtotal colectomy (from the ascending colon to the sigmoid colon) in our department. We had created a stoma at the ascending colon and had closed it 1 year later. During this phase, the patient’s recovery was hampered by nontuberculous mycobacterial infection, for which he underwent treatment with isoniazid, rifampicin, and ethambutol at another hospital; he recovered completely from the infection.
He subsequently presented with repeated episodes of gastrointestinal tract obstruction, even after two surgeries. He was then admitted in our department to receive conservative treatment.
Two years after the first surgery, his central venous port was infected, for which he underwent treatment with antibiotics (sulbactam/ampicillin, vancomycin) at another hospital. Subsequently, he presented with obstruction of the gastrointestinal tract again. We therefore attempted to try and resolve this problem.
Blood tests showed renal dysfunction (serum creatinine level 1.18 mg/dL), anemia (hemoglobin 9.0 g/dL), and a slightly elevated CA19-9 level (46 U/mL). Radiological enteroclysis revealed two stenosed sections of the small bowel (Fig. ). Computed tomography of the abdomen also indicated that the wall of the small bowel was thick and stenosed (Fig. ).
We continued conservative treatment (using an ileus tube), but his condition did not improve. We then decided to operate to resolve this condition.
In the surgery, we recognized two sections of small bowel 30 cm and 53 cm from the terminal ileum seemed to be fibrosed, with extraordinarily thick walls. We resected these sections with a few centimeters margin and anastomosed the remaining bowel using functional end-to-end anastomosis, finally obtaining two specimens (Figs. and ). We also performed tube splinting of the small bowel to prevent further gastrointestinal tract obstruction.
After the surgery, pathological examination yielded a large number of plasma cells and IgG4-positive cells in the specimen; the ratio of IgG4-positive cells to non-IgG-positive cells was 87% (350/404). We then realized that the specimen showed features of IgG4-RD (Fig. ). Based on the diagnostic criteria, this case was classified into the probable diagnosis group.
We then conducted some tests to further clarify the diagnosis of IgG4-related disease. The blood IgG4 level was found to be 52.0 mg/dL, which is within the normal limit. We performed magnetic resonance cholangiopancreatography (MRCP) to detect signs of IgG4-RD in the pancreas and bile duct, but did not find any. We therefore concluded that there were no findings that suggested IgG4-RD, except for in the small bowel.
The patient was discharged to his home on the 39th postoperative day. He has been following up regularly for a year with us and has not shown any symptom of recurrence of IgG4-RD.
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pmc-6311234-1
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A 70-year-old man presented to Aleppo University Hospital in order to have a routine check-up for benign prostatic hyperplasia (BPH) that was diagnosed when he was 31 years old.
Through investigations, we performed an echography of the abdomen and detected a tubular-shaped, moving, echogenic structure with anechoic central line located in the gallbladder; the thickness of gallbladder wall was 4 mm. We did not detect any calculi (). These findings suggest gallbladder ascariasis.
As a history, he had controlled hypertension, a repaired hiatal hernia, gastroesophageal reflux disease (GERD), hemorrhoids, and BPH. However, his general condition was good.
He was asymptomatic, but mentioned that two weeks ago he had experienced nausea, vomiting, hyperthermia, chills, and abdominal pain which started in the right hypochondrial region, radiated to the umbilical region, and lasted for 5 days. The patient did not report jaundice or a change in bowel habit. He dealt with these symptoms himself and took over-the-counter ciprofloxacin, metronidazole, augmentine, and paracetamol.
Multi-slice computerized tomography (MSCT) have not shown any worm or calculi ().
His laboratory findings were all normal including aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (γGT), bilirubin, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), amylase, and complete blood count (CBC). No eosinophilia existed. Ova and parasite (O&P) test was negative.
As the patient is an elderly and hypertensive and was so afraid from operation, conservative treatment was applied with albendazole 400 mg (single dose) and wide spectrum antibiotics, with observation on echography.
After one week, ecography revealed that the worm is still moving and so still alive; therefore, the patient was given a second dose of albendazole.
After 2 weeks, the worm has not appeared on echography, but we noticed an echogenic debris in the gallbladder ().
So, the patient was advised to operate a cholecystectomy to avoid obstruction of bile or pancreatic ducts by the worm's debris, but he disapproved.
The patient returned back to hospital after 10 days; we checked his gallbladder with echography again. It was clear and we did not notice any debris, which means aspiration of the remains of the worm.
After 10 days, he presented to hospital complaining of nausea, vomiting, fever, jaundice, and right hypochondrial pain.
On echography, the common bile duct was not distended and no obstructing structure was noticed.
Laboratory tests revealed leuckocytosis (13800/mm3), with a left shift, as the neutrophils count was 12200/mm3. Eosinophils count was normal. We also found significant increase in CRP (20mg/l), mild elevation in ALT (115 U/L) and AST (90 U/L), and bilirubin was 4mg/dl.
A diagnosis of acute cholecystitis was made, and we perfomed cholecyctectomy for the patient.
There were many adhesions around the gallbladder.
Pathology report confirmed acute cholecystitis. We detected no macroscopic or microscopic remains of the worm in the gallbladder. Under microscope, we noticed a marked number of eosinophils in the bile of the gallbladder.
After three months, our patient is in a good health and has no complications.
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pmc-6311237-1
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A 53-year-old Italian woman came to our attention for a two-year history of progressive lower limbs weakness with difficulty in climbing stairs and posture changes; the patient also complained of occasional difficulty in swallowing. She presented mild hyperCkemia (300 U/L), with isolated occurrence of higher values (up to 1800 U/L) after exercise. Patient's parents were not consanguineous. She had family history of diabetes and cardiac conduction disorders (mother, who died at age 85) and ischaemic heart disease (father, who died at age 90). Her personal history was unremarkable. Neurological examination showed mild proximal weakness of lower and upper limbs and mild neck flexor muscles weakness (MRC 4/5). Forearm ischaemic test revealed basal hyperlactacidemia (42 mg/dL, reference value 4,5-19,8 mg/dl). Electromyography showed a myopathic pattern. Muscular CT showed mild left femoral quadriceps and paravertebral muscles hypotrophy. Cardiological evaluation and spirometry were both normal. Muscle biopsy revealed myopathic changes with scattered ragged red and blue fibers, as well as COX negative fibers (). Ultrastructural examination on muscle confirmed the mitochondrial alterations with mitochondrial hyperplasia and ring cristae, intramitochondrial lipid inclusion, and mitochondria with transversal orientation to the myofiber ().
Muscular mtDNA sequencing showed the heteroplasmic mutations m.5835G>A in MT-TY gene, coding for tRNA Tyrosine. The mutation was heteroplasmic in skeletal muscle; unfortunately, we could not test for the mutation in other peripheral tissues.
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pmc-6311248-1
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A 62-year-old African American woman presented to the emergency department with complaints of abdominal pain, nausea, and vomiting after dialysis. Her history is significant for end-stage renal disease (ESRD) on chronic hemodialysis, morbid obesity, hypertension, type two diabetes, cerebellar vascular accident, and recent bilateral inguinal hernia repair. Her initial workup including computed tomography (CT) scan of her abdomen and pelvis was unremarkable outside of a distended bladder with thickened wall (). Given these findings a Foley catheter was placed for bladder decompression. Over the next twenty-four hours she continued to have ongoing abdominal complaints including nausea and vomiting with worsening clinical picture concerning sepsis in the setting of progressive hypotension (systolic blood pressures in the 70s) and tachycardia (heart rate in the 100s). She had repeat computed tomography scan of her abdomen and pelvis without contrast which was concerning intraperitoneal and extraperitoneal air around the bladder with a Foley catheter in place (). This prompted reevaluation of her bladder further with CT cystogram which demonstrated contrast extravasation (). Within the next twenty-four hours the patient had an exploratory laparotomy which demonstrated pus in the pelvis, necrotic areas of the bladder, and an easily palpated Foley balloon. The patient underwent a partial cystectomy with primary repair. The patient had a complicated postoperative course that included a prolonged intensive care unit stay, postoperative hemorrhage, respiratory failure, sepsis, and pulseless electrical activity cardiac arrest. Given her complicated course the palliative care team was consulted and after multiple family meetings the decision was to pursue comfort care. The patient died shortly after while in hospice care in the palliative care unit.
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pmc-6311255-1
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A 22-year-old male presented to the emergency department with painful swelling of the left hemiscrotum during sexual intercourse. The pain had sudden onset and was located at the left inguinal region. The patient noticed an extending swelling from the left inguinal area through the left hemiscrotum. The medical history revealed bilateral varicocele but no comorbidities or coagulation disorders. On examination, he had a painful swelling starting from the inguinal canal and extending through the entire left scrotum. A soft mass was palpable around the left testis and the spermatic cord. Laboratory tests were within normal range.
Doppler ultrasonography of the scrotum revealed a hematoma extending from the left superficial inguinal ring to the left hemiscrotum, partially surrounding the left testis. No active bleeding was observed (). Both testes had normal structure and blood flow. The presence of bilateral varicocele was confirmed (). Due to the rarity of the condition, an MRI of the scrotum was performed and confirmed the diagnosis of hematoma ().
The patient was treated conservatively with bed rest, ice packs, antibiotics, and analgesics. During the hospitalization he was stable, the pain gradually decreased on the second day and the patient was discharged the third day. Ecchymosis of the scrotum was noticed at the first hospitalization day which gradually disappeared along with the swelling after 4 weeks. Bilateral varicocele repair was uneventfully performed three months later.
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pmc-6311255-2
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A 24-year-old male presented to the emergency department due to left inguinal-scrotal pain which occurred acutely during sexual intercourse. The patient was otherwise healthy without comorbidities or hematological discrepancies. During the physical examination, a mild swelling of the left inguinal region expanding towards the left testis was observed. On palpation, a normal feeling testis but a thickened and painful spermatic cord was found. Laboratory tests were normal.
Doppler ultrasonography of the scrotum revealed a spermatic cord hematoma expanding towards the upper pole of the left testis, with no active bleeding (). Left varicocele was also observed (). The patient refused hospitalization and MRI examination. He was discharged with instructions for bed rest, minimal physical activity, and prescription for analgesics and empirical antibiotic treatment. He returned to the emergency department 24 hours later with mild discomfort and ecchymosis of the left scrotum. A second ultrasound examination was performed showing a reduction of the hematoma and no additional abnormal findings. A follow-up examination was scheduled one week later, but the patient did not appear.
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pmc-6311260-1
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A 48-year-old man with past medical history of COPD on home oxygen, chronic anemia, remote history of polysubstance abuse and alcohol abuse, tobacco use, and chronic kidney disease, PUD gastritis, and GI bleeding, presented to our hospital with complaints of fever, sudden onset nausea, abdominal pain, and hematemesis for 3 days.
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pmc-6311296-1
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In January 2012, a 38-year-old Caucasian woman went to the Emergency Room of the Dunkerque Hospital Center (France), for epigastric pain, no fever, along with jaundice which had been evolving for about a week. Her antecedents were appendectomy, tonsillectomy, and scoliosis with Carrington's stems. The clinical examination noted a swelling of the epigastrium and the right hypochondrium and, above all, a palpable mass was localized at the right hypochondrium. Biochemical analysis showed a liver cytolysis (transaminases: 550IU/L, 10 times greater than the normal threshold), a cholestasis (total bilirubin: 25mg/dl, direct bilirubin: 18mg/dl, indirect bilirubin: 7mg/dl), and an increase in gamma glutamyl transpeptidase: 467IU/L. Lipase and pancreatic amylase were normal.
An abdominal ultrasound was performed and revealed a cystic mass measuring 15 cm x 10 cm, independent of the gallbladder, located between the portal vein confluence and the duodenum. Intracystic gallstone and an intraluminal tissue bud were present at the cystic wall. There was no color flow on Doppler exam in the mass. In addition, there was intrahepatic bile duct dilation, particularly noticeable on the left (). An abdominal-pelvic CT scan was immediately performed, along with an injection of iodinated contrast medium. It showed at portal venous phase the well-defined cystic mass independent of the gallbladder, extended between the confluence of the portal vein and the duodenum, and the intracystic bud that enhances after injection. CT-scan also revealed centimetric hypodense nodules not enhanced after contrast injection in segment VI of the liver and dilation of the left intrahepatic bile ducts. The oblique reconstruction showed the relationship of this cystic mass with the biliary tree (). Biliary MRI indicated the relation between the cystic mass and the bile ducts. The diffusion sequence performed during this examination confirmed the malignancy of the liver's segment VI nodules and the intracystic tissue bud (). The diagnosis of cholangiocarcinoma in a choledochal cyst with hepatic metastases was retained. Transferred to the University Hospital of Lille, the patient underwent a resection of the cystic mass, a cholecystectomy, and a biliodigestive anastomosis.
Histopathological examination of the intracystic tissue bud and of the liver's nodules of segment VI showed an appearance of intraductal and infiltrating adenocarcinoma (). During the patient's hospitalization, GEMZAR CYSPLATINE-type chemotherapy was set up after the multidisciplinary consultation meeting.
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pmc-6311299-1
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A 48-year-old male presented to our hospital with abdominal pain and vomiting. He had no history of prior surgery. His physical examination indicated a body temperature of 37.1°C, blood pressure of 136/61 mmHg, and pulse rate of 94 bpm. He had slight tenderness to palpation over the entire abdomen. His laboratory findings were only significant for an abnormally elevated white blood cell count (14,400/mm3). Abdominal radiography performed in upright position revealed distended loops of small bowel containing gas and fluid in the left upper abdomen and absence of pneumoperitoneum (). Abdominal ultrasonography revealed an apple-shaped foreign body (). Computed tomography was performed without intravenous contrast medium administration. It revealed intestinal obstruction by a 3 × 4 cm foreign body within the right lower abdominal cavity, with dilatation of the small intestine at the proximal side (). Based on this clinical picture, the patient was diagnosed as having small bowel obstruction secondary to a foreign body. An emergency surgery was thus performed.
We performed a 4-cm small abdominal incision by tracing the small intestine from the terminal ileum; further, the site of foreign body was identified by locating the point 40 cm from the proximal side of the terminal ileum. Thereafter, the foreign body was extracted using enterotomy (). The foreign body was a sexual toy designed to attach to the glans penis for the purpose of masturbation (). The toy, having been made of rubber, was extremely soft and compactly foldable. Hence, when swallowed, the toy entered the small intestine and caused an obstruction at the ileum.
The patient experienced surgical site infection after surgery; however, conservative therapy improved his condition within a short period of time. The patient was discharged from the hospital 10 days after the surgery.
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pmc-6311300-1
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A 90-year old Caucasian man came to our department in September 2017 for a routine check-up because of persistent untreated conjunctivitis in his right eye. The patient presented with hypertension treated with amlodipine and furosemide. The ocular history was positive for bilateral primary open angle glaucoma treated with Timolol 0.5%. The patient underwent ectropion surgery five years earlier (right lower lid lateral tarsal strip), bilateral cataract surgery with IOL implantation, and a later YAG-laser capsulotomy. On his left eye, an aponeurotic ptosis was present.
The clinical examination showed a best-corrected distance visual acuity (BCDVA) of 0.7 logMAR (20/100) in the right eye. Intraocular pressure was 20 mmHg in his right eye and 15 mmHg in the left eye. A slit-lamp examination showed conjunctival hyperemia and inferior brownish non-granulomatous endothelial precipitates. The corneal fluorescein staining was negative. The posterior segment did not show any pathological findings.
A viral etiology was suspected and, given that PCR analysis is not available in our clinic, an empirical treatment was started with Ganciclovir gel 1.5 mg/g, 3 times a day. Fourteen days later, the patient presented with a worsening of the clinical condition: BCDVA was hand movement, and he had a corneal paracentral ulcer (1 mm in diameter) with fluorescein staining. The ulceration was surrounded by a mild, localized corneal edema. The Tyndall effect was positive and the precipitates were more numerous.
A corneal scraping was then performed, and the clinical manifestation was highly suspected to be a fungal keratitis. Therapy was modified with 2 mg/ml topical voriconazole 1% 4/die and moxifloxacin 0.3% 6/die.
The cultural test on Sabouraud agar gave a diagnosis of Aspergillus niger infection. Despite the therapy modification, the corneal situation continued to worsen, with a perikeratic injection and increased size of the round corneal ulcer (4 mm in diameter) involving the optical zone and reaching the deep stroma () with massive melting and surrounding edema. AS-OCT images were not able to detect the effective pachymetry of the residual stroma because of the corneal melting.
The literature has reported promising results with CXL as adjunct therapy for fungal keratitis. Because the clinical condition became worse with antifungal therapy, and since we obtained A. niger positivity, we planned a CXL-WA [] 7 days after corneal scraping. Informed consent was collected from the patient.
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pmc-6311301-1
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A 40-year-old Chinese man had a history of ST-segment elevation inferior myocardial infarction 6 months earlier. He received primary PCI therapy at another hospital. Following predilation with a 2.0 × 20-mm balloon at 12 atm for 6 seconds, a 3.5 × 24 mm sirolimus-eluting stent (EXCEL, JW Medical Systems, Shandong Province, China) was implanted in the lesions of the proximal RCA. However, after stent implantation, coronary angiography (CAG) showed TIMI grade 0 flow in the RCA (Fig. ). He did not receive further PCI therapy because he had no persistent chest pain at that time. He was prescribed regular dual anti-platelet (PLT) therapy with aspirin and clopidogrel, as well as statin treatment.
Six months later, he was admitted to our hospital for recurrent unstable angina. He denied a history of hypertension, diabetes mellitus, and valvular heart disease. He also denied being allergic to pollen, dust medications, or food, and surgical procedures and injuries. He was married at the age of 23 years and he had one boy and one girl. He received aspirin (0.1 g per day) and clopidogrel (75 mg per day) prior to admission. He had smoked 20 cigarettes per day for 10 years, and had drunk a little amount of alcohol for 20 years.
A physical examination showed: temperature (T) 36.4 °C, pulse (P) 85/minute, respiratory rate (RR) 20/minute, and blood pressure (BP) 130/80 mmHg. He was well developed, moderately nourished, and active. His skin was not stained yellow, with no cyanosis, pigmentation, skin eruption, or spider angioma. There was no pitting edema.
A heart examination revealed no bulge, abnormal impulse, or thrills in precordial area. The border of his heart was normal, and the point of maximum impulse was in his fifth left intercostal space inside the mid clavicular line and it was not diffuse. There was no pericardial friction sound. His heart sounds were strong and there was no splitting. His cardiac rhythm was regular with no pathological murmurs.
A neurological examination showed normal abdominal, bicipital muscular reflex, patellar and heel-tap reflex with Babinski sign (−), Oppenheim sign (−), Gordon sign (−), Chaddock sign (−), Hoffmann sign (−), Kernig sign (−), and Brudzinski sign (−).
An electrocardiogram (ECG; 24 October 2017) in our hospital showed that deep Q waves were present in the II, III, and aVF leads, suggesting old lower wall myocardial infarction. An initial echocardiogram revealed a left ventricular ejection fraction (LVEF) of 41%.
Laboratory findings (25 October 2017) in our hospital showed: red blood cells (RBC) 4.41 × 1012/L, white blood cells (WBC) 5.81 × 109/L, N 71.9%, hemoglobin (HGB) 133 g/L, PLT 225 × 109/L, aspartate aminotransferase (AST) 10.5 U/L, alanine aminotransferase (ALT) 11.7 U/L, creatinine (Cr) 7.2 mmol/L, and blood urea nitrogen (BUN) 102 umol/L. Cardiac biomarkers of troponin T (TnT), creatine kinase (CK), and isoenzyme of CK (CK-MB) were negative.
A repeat CAG showed that although the proximal edge of the previous stent exhibited total occlusion, flow into the distal RCA through another pathway could be seen. The JR4.0 guide catheter was placed immediately outside the ostium of the RCA, and we adjusted the direction of the guide wire to direct it from the ostial true lumen into the distal RCA. Then, IVUS was performed to confirm that the previously deployed stent was in the false lumen, resulting in stent occlusion, and that this guide wire did not go through the struts of the previous proximal stent [, ]. A balloon (Sprinter 2.0 × 20 mm, Medtronic, Minneapolis, Minnesota, USA) was then predilated at 14–16 atm to crush the previous stent. Another 4.0 × 20 mm stent (BuMA™, SINOMED, Tianjin, China) was deployed in the true lumen of the proximal RCA to crush the previous stent, followed by postdilation with a 4.0 × 12 mm balloon at 16–18 atm. Blood flow into the RCA finally recovered to TIMI grade III (Fig. ). Another 12 months of dual anti-PLT therapy was recommended to prevent stent thrombosis and restenosis. Our patient completed his 6-month and 9-month out-patient follow-up visits with no complaints of discomfort (Table ).
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pmc-6311313-1
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A 68-year-old male presented to the emergency department with progressive weakness, intermittent confusion, and falls. Past medical history was significant for coronary artery disease, peripheral vascular disease, hypertension, diabetes mellitus, and liver cirrhosis secondary to Wilson's disease. Physical exam revealed a lethargic but oriented patient with jaundice, superficial skin abrasions on arms, bilaterally diminished breath sounds, grade 2/6 systolic murmur, and lower extremity edema.
The patient was admitted for management of acute renal failure and hepatic encephalopathy. Complete metabolic profile revealed elevated ammonia of 186 μmol/L (12-60 μmol/L), serum creatinine of 6.8 mg/dL (0.7-1.2 mg/dL), blood urea nitrogen of 134 mg/dL (8-20 mg/dL), total bilirubin of 3.0 mg/dL (0.4-2.0 mg/dL), aspartate aminotransferase of 97 U/L (15-41 U/L), alkaline phosphatase of 318 U/L (38-126 U/L), and albumin of 2.4 g/dL (3.5-4.8 g/dL). Hematology and coagulation studies showed hemoglobin of 12.9 g/dL (12.5-15.5 g/dL), thrombocytopenia (platelet count of 55,000; 150,000-400,000 normal), neutrophilia (79.7%; normal range 37-73%), monocytosis (13.3%; normal range 3.0-10%), lymphocytopenia (6.3%; normal range 20-55%), high red cell distribution width of 19.7% (11.0-15.6%), and elevated activated partial thromboplastin time of 39 seconds (normal range 26-34 seconds). Serologic studies for hepatitis virus were negative. Cardiac enzymes were unremarkable. The laboratory values for lactate dehydrogenase (LDH), soluble interleukin-2 receptor, beta-2 microglobulin, and ferritin were not available. Computerized tomography scan of the head revealed no acute intracranial changes.
The patient was placed on hemodialysis and lactulose with serial monitoring of ammonia levels. His clinical status improved slightly after dialysis but showed no sustained clinical improvement. On the 6th hospital day, the patient was intubated following worsening oxygenation and severe hypotension and expired the following day. A complete postmortem examination was performed.
At autopsy, the patient had jaundice, bipedal edema, hepatomegaly (weight = 2219 grams) with diffuse micronodular cirrhosis, and splenomegaly (weight = 907 grams), consistent with liver failure. He had moderate cardiomegaly (weight = 533 grams) with marked concentric left ventricular hypertrophy and bilateral nephrosclerosis, consistent with long-standing hypertensive cardiovascular disease. Upon microscopic examination, numerous large atypical lymphoid cells were found within the lumen of several small blood vessels of the thyroid gland (Figures and ), lungs (), omentum (), gallbladder (), peripancreatic tissue, and pericolonic fat. These cells were large in size, with round to somewhat irregular hyperchromatic nuclei with occasional prominent nucleoli (). Immunohistochemical staining performed on thyroid gland revealed a B-cell phenotype (positive for CD20 (), dim CD79a (), and dim PAX-5 and also positive for MUM-1 (), CD5 (), and dim CD30. CD10 (), BCL-2, c-MYC, HHV8 (), BCL-6, CD3, CD138, and cyclin-D1 were negative. Epstein Barr virus (EBV)-encoded small RNAs (EBER) by in situ hybridization was negative (). This phenotype supported nongerminal center phenotype of large B-cell lymphoma. Ki-67 showed nuclear staining in approximately 60-70% of cells. The vessels of the spleen and liver were not involved by the lymphoma. There was no involvement of the skin, bone marrow, or peripheral blood. Neuropathologic examination showed mature central nervous system with no specific histopathologic findings. Overall, the histomorphologic features and immunoprofile were consistent with IVLBCL. The clinical, laboratory, and autopsy findings demonstrated that the most likely cause of death was hepatorenal syndrome due to liver cirrhosis complicated by IVLBCL diagnosed at autopsy.
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pmc-6311398-1
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A 9-year-old male patient accompanied by his mother sought dental assistance complaining of a palatal swelling. The lesion was painless and had initially been observed 5 months earlier. The medical history was noncontributory.
The intraoral physical examination revealed a 10x5 mm, ill-delimited, firm and sessile nodule, located in the palatal mucosa of the left central incisor (Fig. A,B). The overlying mucosa was intact and normal in color. Buccoversion of the adjacent teeth was observed, but no mobility or other periodontal alterations.
Panoramic, occlusal and periapical radiographs did not show alterations in the area adjacent to the lesion (Fig. A-C). A cone beam computed tomography (CBCT) exam also revealed no related bone alterations, but show a slight soft tissue swelling located in the palatal mucosa of the left maxillary central incisor (Fig. D).
The main diagnosis hypotheses included fibrous hyperplasia, peripheral ossifying fibroma, pyogenic granuloma and peripheral giant cell granuloma. An excisional biopsy was performed under local anesthesia. During the lesion’s surgical removal, no superficial bone resorption was observed. Grossly, a cyst-like structure was observed adhered to the oral mucosa. The sample was sent to a Pathology Laboratory.
The histological examination revealed an oral mucosa fragment covered by a stratified squamous keratinized epithelium showing areas of hyperplasia (Fig. A). A cystic lesion was observed adhered to the deeper lamina propria (Fig. A-D). The cystic capsule, formed by dense fibrous connective tissue, was lined by an ameloblastoma-like epithelium (Fig. E). The basal layer cells of this lining epithelium were cubic or columnar, showing reversed polarity and hyperchromatic nuclei, disposed in palisade. The cells of the suprabasal layers were sometimes loosely arranged. Enlarged epithelial cells with eosinophilic cytoplasm and no nucleus (ghost cells) were sporadically found in the lining epithelium (Fig. E,F) and abundantly observed in the cyst lumen (Fig. C,G). Calcification of ghost cells was also observed (Fig. C-F). Juxtaepithelial dentinoid could be seen in the cyst capsule (Fig. E). Moreover, soft and hard dental tissue resembling a developing odontoma were observed in the cyst wall (Fig. C,H).
The diagnosis of peripheral COC was established. In a follow-up visit two months after the excisional biopsy, the area was adequately healed (Fig. C). One year after the surgical removal, no recurrence was observed (Fig. D). The patient has been disease-free for 5 years. Informed consent has been obtained by the patient.
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pmc-6311403-1
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A 51-year-old male patient was referred to Hospital Municipal Rolim de Moura, Brazil, with chief complain of swelling and skin lesion in the region of right angle mandible, after a trauma during the feed, with two years of evolution. Consequently, severe trismus, limited mouth opening (approximately 10mm) and speaking difficulties were observed. The patient had the habit of smoking for 40 years and alcohol consumption for 30 years. Panoramic radiograph revealed edentulous maxilla and mandible, presenting a multilocular osteolytic radiolucency that expanded and perforated the bone cortical, with irregular and indefinite margins, extending from mandibular angle into ascendant ramus. The mandibular angle was almost entirely occupied by lesion (Fig. ). Extra-oral examination revealed swelling in mandible right region and an ulcerated area in cutaneous region. Fine needle aspiration was negative and an incisional biopsy was performed. Clinical hypothesis was of osteosarcoma or benign odontogenic tumor. Microscopic analysis showed cystic formations and nests of intermediate epithelial neoplastic cells with mucous and epidermoid appearance, inside the viable compact bone extending into surrounding soft tissue. Some of the malignant cells presented moderate pleomorphism and discrete hypercromatism. The cystic spaces were lined by mucous secreting cells positive for periodic acid-Schiff staining (Fig. ). Based on clinical, radiographic and microscopic features, the final diagnosis was of intraosseous low grade mucoepidermoid carcinoma. The patient was submitted to surgical partial mandibulectomy including the removal of part of the tongue, floor of the mouth and ipsilateral neck dissection of the lymph node. The histopathological analysis of the surgical specimen confirmed intraosseous low grade mucoepidermoid carcinoma, with surgical margins and lymph nodes free of the tumor. Six months after tumor resection, the patient was submitted to another surgery with rotation of pectoral flap, due to bone exposure. Adjuvant radiotherapy was prescribed for sixty days. Three-years follow-up showed no sign of tumor recurrence and the patient is being accompanied for rehabilitation (Fig. ).
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pmc-6311407-1
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A 62-year-old female patient was referred by her oncologist for a routine dental evaluation. The patient’s medical history revealed a cutaneous melanoma of the left dorsum diagnosed six years before she was referred to our dental service. The tumor was primarily treated by surgery and developed two local recurrences (one and three years following surgery, respectively), which were also managed by surgical resection. Disease progression was identified five years after the first treatment and confirmed by a computed tomography (CT), which revealed multiple organ involvement including the lungs, skin (subcutaneous nodules on the dorsum) and bone (osteolytic lesions in the iliac and femur bones, ribs, vertebrae, sternum and scapula).
The patient was undergoing a palliative treatment protocol based on dacarbazine, zoledronic acid and radiotherapy in the lumbar region (total dose of 20 Gy) and in the left supraclavicular fossa (total dose of 36 Gy) when she was referred to our dental facility. An extraoral clinical examination identified a pigmented subcutaneous nodule on the patient’s dorsum, measuring 5 cm in diameter, and scarring from the previous surgical resections.
The patient’s chief complaint was the loss of the dental crown of her upper left incisor. She denied oral pain or the existence of any relevant oral soft tissue lesion. Intraoral soft tissue examination revealed a nodule with an ulcerated surface and areas of telangiectasia, on the posterior left lateral border of the tongue, measuring approximately 1 cm in diameter, adjacent to a partial edentulous mandibular area (Fig. A). Based on the clinical features of the tongue lesion and on the patient’s medical background, the diagnostic hypothesis included metastatic melanoma, squamous cell carcinoma and fibrous hyperplasia.
An incisional biopsy was performed under local anesthesia. The histopathological analysis showed nests and solid sheets of non-pigmented atypical cells with an epithelioid phenotype infiltrating the sub-epithelial connective tissue. A high mitotic index was observed (Fig. B). Tumor cells displayed diffuse immustaining for S100 protein. Other melanocytic markers such as HMB-45 and Melan-A were negative. (Fig. C).
After the diagnosis of a metastatic lesion on the tongue, the patient was referred back to the clinical oncologist who maintained her in a palliative protocol of chemotherapy with cisplatin, dacarbazine and vinblastine (CVD). Unfortunately, the patient died due to disease progression four and a half months after the diagnosis of tongue metastasis.
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pmc-6311407-2
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A 62-year-old female was diagnosed with an acral lentiginous melanoma on the right heel four years previously. At that time, CT revealed pulmonary nodules and the patient was kept in close follow-up. Two years after the initial diagnosis, the patient was submitted to a pulmonary biopsy with a diagnosis of metastatic melanoma. Four months later, the patient requested a dental evaluation due to a fast-growing submucosal nodular lesion on her tongue.
During the first dental appointment, intraoral soft tissue examination revealed a submucosal nodule in the right dorsum of the tongue measuring approximately 2 cm in diameter and firm upon palpation (Fig. A). The patient reported three months of painless nodule progression. Based on the previous medical history of the patient, the diagnostic hypothesis included metastatic melanoma and benign mesenchymal neoplasm.
An intra-oral incisional biopsy was performed under local anaesthesia. The histopathologic analysis was characterized by proliferation of atypical epithelioid cells displaying a poorly delimited cytoplasm and hyperchromatic nucleus which contained eosinophilic macronucleoli (Fig. B). Immunohistochemistry showed multifocal staining for melanocytic markers, including S100 (Fig. C), HMB-45 (Fig. D) and Melan-A (Fig. E). These findings confirmed the clinical hypothesis of metastatic melanoma.
After diagnosis, the patient was referred back to the clinical oncologist who investigated a left subclavicular mass with a diagnosis of metastatic melanoma and also presented disease progression to the lungs, retroperitoneal region and central nervous system. The patient died 20 months after the diagnosis of oral metastatic melanoma even though she was under palliative care and careful medical follow-up.
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pmc-6311408-1
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A 16-year-old man with no systemic diseases, resident of the city of São Lourenço, Rio Grande do Sul, Brazil, sought a dental surgeon for the endodontic treatment of the tooth 47. Radiographs were requested in December 2004 and was observed a well delimited unilocular lesion associated with impacted tooth 48 (Fig. ). The man was referred to a specialist in oral and maxillofacial surgery in the city of Pelotas, RS, before endodontic treatment.
The marsupialization of the lesion and an incisional biopsy was performed and histologic analysis revealed dentigerous cyst. Three months later the endodontic treatment of the tooth 47 was made. After nine months, the lesion was completely removed and the biopsy was sent for histopathological analysis in Center of Diagnosis of Diseases of the Mouth, Federal University of Pelotas, Brazil (CDDB-FO / UFPEL). Histologic analysis revealed unycistic mural ameloblastoma (Fig. A-C). Approximately 3 months after tooth 48 extraction and total removal of the lesion, it was possible to observe a mineralize d aspect compatible with the normal repair process of the region. Patient was followed up every 12 months. The tooth 47 was extracted. Currently, the patient is clinically healthy. In panoramic x-rays at 5 (Fig. A) and 13 years (Fig. B) after diagnosis it is possible to observe evidence of bone repair.
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pmc-6311725-1
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A 34-year-old man without a previous medical history was referred to our endocrinology clinic due to an eight-month history of generalized fatigue, increased thirst, increased urinary frequency and volume, reduced nocturnal erections, and decreased sexual desire. Additionally, he reported a weight loss of 18 kg in six months, dry skin, cold intolerance, and constipation during the same period. He did not report any headaches, vision problems, recent head trauma, use of illegal substances, family history of pituitary diseases, or close contact with anyone sick. At the time of his referral, therapy with cortisone acetate 25 mg twice daily and levothyroxine (LT4) 50 mcg daily had already been initiated by his primary care physician.
At the initial visit, physical examination revealed normal vital signs and a delayed tendon reflex of the deep tendon reflex in the upper/lower extremities. The first set of serum and urine laboratory examination results revealed hypopituitarism, hypogonadotropic hypogonadism, polyuria, and hypertonic hypernatremia. The first magnetic resonance imaging (MRI) scan showed a right-sided pituitary microadenoma (3 mm). No suprasellar mass or compression of the optic chiasm was noted. Steroid therapy was changed to hydrocortisone 10 mg/5 gm and levothyroxine replacement was optimized by weight. Follow-up serum laboratory and imaging studies were ordered.
A second MRI, one month later, revealed an abnormal thickening of the infundibulum with no evidence of the microadenoma (). New laboratory examination results confirmed the previous findings and ruled out the presence of an autoimmune or inflammatory condition (). Tumor markers for germ cell tumors were negative. A water deprivation test confirmed central diabetes insipidus. A chest X-ray was unremarkable for masses or infiltrative lesions. Testosterone replacement and desmopressin (DDAVP) were added.
Due to nonspecific imaging findings, a negative X-ray, and no evidence of systemic disease, a conservative approach with prednisone was taken. However, six months later, the stalk lesion worsened. At that time, the patient underwent transsphenoidal surgery for a tissue biopsy. The tissue was positive for an intrasellar pituitary germinoma, confirmed by positive human chorionic gonadotropin (hCG) staining, C-kit, and placental alkaline phosphatase (PLAP) (). A lumbar MRI scan and a lumbar puncture were negative for metastatic disease. Treatment with whole ventricle brain radiation was started, with subsequent clinical improvement.
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pmc-6311753-1
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A 7-year-old boy presented to the otolaryngology sleep medicine clinic after being referred by his neurologist for OSA (Video 1). His past medical history was significant for a traumatic brain injury suffered after a dog attack during infancy, resulting in neurologic developmental delay, posttraumatic stress disorder, and attention deficit hyperactivity disorder. He underwent a polysomnogram prior to evaluation, which showed mild OSA with an AHI of 1.7, rapid eye movement (REM) AHI of 6.3, and a low oxygen saturation of 92%. On clinical examination, his tonsils were noted to be a +3 size (75% of oropharyngeal airway) on the Brodsky scale, but there was clinical concern that there may be additional sites of obstruction. He underwent a DISE with T&A one month later, and on postoperative follow-up, his mother did not believe his snoring had improved.
A few months later, based on initial DISE findings of a retroflexed epiglottis with lingual tonsil hypertrophy, he underwent an epiglottopexy with lingual tonsillectomy. A postoperative sleep study performed three months after that surgery (and five months after T&A) was concerning for worsening OSA (AHI 4.5; REM AHI 12.1; low O2 saturation 94%). He underwent a second postoperative DISE four months after that polysomnogram, which showed complete collapse of the base of the tongue against the posterior pharynx. When compared to his preoperative DISE prior to T&A, it became apparent that the tonsils were likely not obstructing at the time, but splinting the airway open. The patient was scheduled for a posterior midline glossectomy but was lost to follow-up.
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pmc-6311754-1
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A 27-year-old man presented with severe pain on the right carpus following a fall with injury to the right hand. There was mild swelling of the fourth and fifth CMC joint region, and a bony prominence was felt dorsally. Furthermore, there was apparent shortening of the fourth and fifth rays (Figures and ). A diagnosis of the fourth and fifth CMC joint dislocation was made based on radiographs and computed tomography scans. Anteroposterior, lateral, and internal oblique radiographs of the right hand showed dorsal dislocation of the fourth and fifth CMC joints, without fracture (Figures –). Immediate closed reduction was done in the operating room under locoregional anaesthesia by applying longitudinal traction and direct pressure on the metacarpal base dorsally. However, the achieved CMC joint reduction was unstable and easily dislocated dorsally on passive flexion of the metacarpal joint. Finally, we decided to perform external fixation using an Ichi-Fixator (Neo-medical, Saitama, Japan) linked-wire external fixator. Before the operation, the quick disabilities of the arm, shoulder, and hand questionnaire (QDASH) score were 52.95 and the visual analogue scale (VAS) pain score was 5/10.
After closed reduction, a 1.5 mm fixator pin was inserted from the base of the fifth metacarpal to the third metacarpal transversally (). Another 1.5 mm fixator pin was inserted from the ulnar base of the fifth metacarpal to the hamate bone obliquely (). The external ends of the two pins were bent so that they became parallel. The parallel ends of the two pins were then inserted in a metal clamp from opposite sides (). After fluoroscopic assessment, the ends of the two pins were fixed firmly together using a clamper (Figures and ). A light dressing was applied, and the patient was allowed to start range-of-motion exercises without immobilization immediately after the operation. The patient could use the hand for light activities just after the operation and could return to his regular work 3 days after the operation. The pins were removed in an outpatient setting when union of the fracture was verified radiologically. In the current case, the linked-wire external fixator was in place for 6 weeks. At the most recent follow-up, the QDASH score was 0.00 and the VAS score was 0/10. The grip strength and total active motion were 102% and 101%, respectively, compared with the contralateral side (Figures –). The patient could perform all routine activities with normal grip strength and a full range of hand motion without pain. The patient could carry out his previous work just as before. He showed no pain and returned to all his previous activities without discomfort.
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pmc-6311759-1
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A 79-year-old lady presented to the Emergency Department with a painless anterior neck swelling. The swelling appeared one day before and was gradually increasing in size. She first noticed the swelling after she removed her dentures in the evening. Several hours later, she developed hoarseness of voice, odynophagia, and mild shortness of breath. There was no hematemesis, melena, or any neurological deficits. On further questioning, she had a history of hypertension and atrial fibrillation. She has been taking amlodipine and warfarin but was not compliant to her medication and follow-ups. She was supposed to be on warfarin of 3mg per day. However, she did not present herself to the clinic for warfarin optimization, and no INR was done.
On examination, she was fully conscious. However, an audible stridor was heard. Her blood pressure was 130/90mmHg, heart rate 92/min, respiratory rate 24/min, and oxygen saturation 95% on room air. There was a large submandibular swelling at the anterior side of her neck. The mass extended to the left side of neck and was 8cm by 6cm in size. The skin overlying the swelling was bluish-red, and there was tenderness on palpation. Upon mouth opening, there was a hematoma at the base of her tongue which extended to both sides of the tonsillar pillars. The uvula appeared edematous and engorged. There was limitation in mouth opening due to the pain. Bleeding was seen from the base of the tongue when her tongue was protruded.
Blood investigations revealed hemoglobin of 12.4g/dl, platelet 274 x 109/liter, with normal electrolytes. The Prothrombin Time (PT) and Partial Thromboplastin Time (PTT) were prolonged for more than 2 minutes and INR was 8.0. A flexible nasoendoscopy done by the otorhinolaryngologist found a huge swelling at the laryngeal area. The vocal cords were not visible. There were blood clots covering both the arytenoids and epiglottis.
The patient was planned for tracheal intubation due to her worsening respiratory distress. Intravenous vitamin K and fresh frozen plasma (FFP) were given immediately.
Anaesthetic management at that time was gas induction with Sevoflurane in incremental concentration until loss of consciousness with preservation of spontaneous breathing. Muscle relaxants were not used. A D-blade video laryngoscope CMAC was used. During intubation, it was noted that the laryngeal apertures were grossly engorged and swollen. The oral structures were beyond recognition. Blood clots were seen covering the pharyngeal walls, epiglottis, and arytenoids. The vocal cords were not prominently visualized. As the patient was spontaneously ventilated, air bubbles were seen from the posterior side of the engorged epiglottis. This served as a guide for tracheal tube insertion (). A size 6 endotracheal tube was used to secure the airway. It was a successful intubation only at the second attempt. Hemodynamics were stable throughout the procedure.
The patient was sent to the ICU for ventilation and observation. The hematoma at the neck and base of tongue subsided after 2 days. Her INR was 2.0, and she was discharged from the ICU soon after that.
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pmc-6311773-1
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A 27-year-old female patient presented with recurrent left-sided, lower back and left gluteal pain for 6 months. The lower back pain increased with long periods of sitting or standing, whereas the gluteal pain was most intense when changing positions, particularly when standing from a sitting position. Both types of pain improved partially with walking. One month prior to visiting the clinic, she noticed occasional numbness in the left thigh. She showed a partial temporary response to nonsteroidal anti-inflammatory drugs (NSAIDs). Neurological examination was normal, except for pain on spinal extension and axial rotation, with tenderness over the lower lumbar paraspinal region and left sacroiliac joint (SIJ) region. She underwent a lumbar stress X-ray (LSS-X-ray), sacroiliac joint X-ray, and lumbar MRI which showed moderate left L5/S1 posterolateral disc prolapse. Her pain score was described as 8/10.
The clinical picture of this patient can suggest facet joint pain or sacroiliac joint (SIJ) pain, whereas the MRI findings showed intervertebral disc (IVD) herniation. It is important to note that the image changes for facet and sacroiliac joints do not correlate with the pain experienced by the patients. Consequently, normal images cannot exclude facet or SIJ as pain generators. Therefore, diagnostic injections are the only confirmatory tests. Facet joint pain is mediated with the medial branch of the dorsal rami where each facet joint is innervated with two medial branches: from the level above and the same level (i.e., L3/4 facet is innervated with L2 and L3 medial branches). Hence, a diagnostic medial branch block should involve the two supplying medial branches. The L4 lateral branch, L5 dorsal ramus, and S1,2,3 lateral branches innervate SIJ posteriorly. The presence of disc herniation could be coincidental, as the expected radiculopathy and radicular pain were both absent. Patient underwent diagnostic L3 and L4 medial branch (for the L4/5 facet), L5 dorsal ramus, and S1,2,3 lateral branch blocks. The pain VAS score dropped to 2/10 which confirmed the diagnosis of facet joint and SIJ pain. Selective nerve root block, which was planned if the patient's responses were negative for medial and lateral branches blocks, was canceled since a positive response was obtained. The patient was referred for physiotherapy, with a plan for radiofrequency if symptoms recurred.
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pmc-6311773-2
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A 54-year-old male patient presented with a two-day history of severe left-sided, lower back pain which disappeared with the appearance of left-sided lower limb pain felt deep inside the whole lower limb and described by the patient as intense internal pressure (VAS 8/10). On examination, power was 5/5 with no sensory deficit and normal reflexes. The patient received NSAID painkillers and active bed rest was advised. However, on the patient's insistence, a lumbar spine X-ray and MRI were done which showed mild IVD protrusion. The patient was reassured and sent home. A week later the patient presented to the ER with an 18-hour history of heaviness and difficulty in raising the left foot when walking, with numbness along the lateral part of the leg and dorsum of the foot. The pain was moderate (VAS 5/10). No sphincter-related symptoms were observed. According to the patient, the decreased pain caused the delay in presentation, against the instructions on first evaluation. On examination of the foot dorsiflexion was 2/5 (movement on gravity alleviation) with decreased sensation along the left L5 dermatome. There were normal reflexes and sphincters. The patient underwent immediate, new lumbar MRI which showed a large disc sequester with disc migration. His status was fully explained; he was admitted and underwent microdiscectomy L4/5.
The initial back pain lasted for 2 days, mostly caused by stretching and pressure on the weakened annulus fibrosis. This type of pain disappears or decreases once the annulus opens and nucleus pulposus leaks to the spinal or root canal. Initial left lower limb pain is a typical description of painful radiculopathy where mass pressure and inflammatory irritation of the nerve root and dorsal root ganglion cause neuropathic pain. This is different from nociceptive and referred pain types. Dorsal root ganglion hosts the cell bodies of sensory nerves with bidirectional connections (to the periphery and spinal cord). Injury to the nerve root motor fibers causes weakness.
The majority of patients with lumbar disc and radicular pain improve with conservative treatment. Surgical indications are acute or progressive motor weakness, sphincter dysfunction, intractable pain not responding to analgesia, and pain affecting patient daily life, not responding to 6 weeks of conservative treatment in the absence of acute surgical indications. In all cases, there should be a correlation between the clinical picture and MRI findings. In the current case, the patient has left L5 nerve root symptoms and signs (dorsiflexion weakness, normal reflexes, and dermatologic radiculopathy). The expected IVD prolapse occurred on either the left posterior-lateral L4/5 or left extreme lateral L5/S1 disc. Although there is a debate about dermatologic sensory distribution in root-originating symptoms and variations in clinical presentation (i.e., the L4/5 disc causing S1 root symptoms via compressing the root in higher position, groin pain with lower lumbar discs due to paravertebral sympathetic ganglion pathway entering at L1 or L2 nerve), we presented the commonly encountered scenarios.
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pmc-6311773-3
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A 70-year-old female patient presented with recurrent lower back pain (LBP) which worsened during the last 6 months. The pain increased with changing position and did not improve with walking. Alternating pain radiated to the gluteal region, thighs, and legs with pain in the left more than the right side (VAS for LBP 9/10, for lower limb pain 3/10). Examination showed only decreased sensations in the L5 dermatomal distribution. The patient underwent a lumbar MRI and stress X-ray which showed L4/5 degenerative spondylolisthesis grade 2. Instrumental fusion and decompression were initially planned, but both the patient and family declined surgical intervention. She was offered a palliative solution of a medial branch block which showed a good response (VAS for LBP decreased from 9 to 2). The patient was referred for physiotherapy, prescribed a lumbar belt and painkillers, and scheduled for radiofrequency on symptom recurrence.
Spondylolisthesis refers to the forward or backward slippage of one vertebra on an adjacent vertebra. Isthmic spondylolysis and spine degeneration are the most common causes. The first involves a defect in pars interarticularis occurring in young athletes, whereas the latter occurs due to degenerative facets in older subjects and, possibly, an increase in sagittal-orientated facet joints. Degenerative spondylolisthesis tends to be asymptomatic and self-limiting. Hence, surgery is reserved for patients with significant pain affecting daily life. Pain generation could arise from mechanical instability and/or nerve compression. Consequently, in the absence of central or lateral canal stenosis or significant symptoms, pain can be approached via minimal interventions, mainly medial and lateral branch blocks and radiofrequency. It should be noted that two diagnostic injections are needed to confirm the pain source. However, in the current case, the aim was palliative pain treatment and we considered a single injection enough.
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pmc-6311773-4
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A 48-year-old female patient presented with recurrent neck pain extending to both shoulders, affecting her daily activity and sleep. She responded partially to physiotherapy and painkillers. On examination, there was muscle spasm mainly in the upper trapezius with limitation to neck extension, lateral flexion, and rotation. She underwent a cervical X-ray and MRI which showed two moderate IVD protrusions at C4/5 and C5/6. The patient underwent percutaneous discectomy for both discs under local anesthesia and sedation. Referred pain to upper limbs and shoulders disappeared the same day (VAS dropped from 5 to 1), whereas neck pain decreased significantly (VAS dropped from 8 to 2). For 3-18 days, the patient reported intermittent attacks of neck pain (VAS 6/10) but not referred pain. After 18 days her axial neck pain showed mild improvement (VAS 4/10). She began physiotherapy for strengthening deep muscles and relaxing extrinsic muscles and showed good improvement for 4 months.
The initial pain improvement could be attributed to decreased disc pressure. Referred pain arises from any of the pain generators in the same spinal segment. However, axial neck pain could be single or a combination of discogenic, facet joint, and/or myofascial pain. Asymptomatic spine degeneration is common and nonlocalizing for nociceptive pain; therefore, diagnostic injection and discography correlation with patient axial pain and image findings are necessary. Discography is done as part of the percutaneous discectomy, and it requires the patient to be fully awake, which could be difficult to accomplish in cervical procedures. Consequently, discography is a confirmatory test in image-guided percutaneous procedures which form a bridge between conservative and classical surgical interventions. The current patient may need a medial branch block on axial pain recurrence.
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pmc-6311773-5
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A 42-year-old female patient presented with neck pain, right brachialgia, right occipital pain, and right-sided pain radiating to the frontal and periorbital region for 8 months. Pain attacks occurred 3-5 times weekly with variation in intensity for each pain component (average VAS 7/10). The patient was on painkillers and treatment for a migraine. Physical examination showed decreased sensation along the right C6 nerve distribution, tender neck muscles with limited neck movement, and trigger points with referred myofascial pain to the occipital, frontal, and periorbital region. Cervical MRI showed multiple small disc protrusions and a moderate disc at right C5/6. The patient underwent surgical treatment for the C5/6 disc which relieved her symptoms including occipital, frontal, and periorbital pain.
The current patient presented with axial, referred, and radicular pain, but the hemisided headache similar to a migraine was different. Cervicogenic headache is pain perceived in the trigeminal region caused by changes in the bony or soft neck structures. Though cervicalgia is reported with lower cervical discs, a debate about the mechanism still exists, and it is occasionally mistaken for a migraine or trigeminal neuralgia. Possible mechanisms and the author's personal scientific opinion are included for completion in the discussion.
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pmc-6311773-6
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A 38-year-old female office worker presented with pain at the coccygeal region (tailbone) recurrent for 6 months with short periods of pain relief during vacation. Her pain increased with sitting on a hard object and did not respond to conservative treatment. There was no neurological deficit. X-ray showed type I coccyx (curved slightly forward). She underwent fluoroscopic guided impar ganglion block (sacrococcygeal approach) and showed good improvement. A coccygeal pillow was advised.
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pmc-6311773-7
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A 29-year-old female patient presented with a 6-week coccygeal region (tailbone) pain after falling during cycling. The pain was intense for the first 3 weeks and then improved with NSAID. X-ray showed a type III coccyx (curved sharply and angulated forward). Continued conservative treatment and use of a coccygeal pillow were advised.
Coccydynia refers to pain in and around the coccyx that can arise after major trauma (Case 7) or repetitive minor trauma (Case 6). It is a clinical diagnosis that has no definite correlation with X-ray findings. An impar ganglion block is indicated in coccydynia failing conservative treatment. Cases 6 and 7 emphasized that the clinical response, not the X-ray findings, guides treatment even in the presence of coccyx type IV on X-ray (coccyx fracture or subluxation).
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pmc-6311775-1
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A 59-year-old male was admitted to our ward with abdominal pain in the right upper quadrant, nausea, and vomiting; the symptoms had started about 24 hours before. Physical examination showed tenderness of the abdomen, positive Murphy's sign, negative Blumberg's sign. On admission, blood test showed WBC count of 17.200/mm3, whereas liver function tests, lipase, and amylase levels all resulted as normal. Abdominal ultrasound showed a single gallstone impacted in the infundibulum of a dilated gallbladder, with a thick and inflamed wall. The patient underwent emergency laparoscopic cholecystectomy. A three-trocar technique was used inserting the cannulas in the umbilicus (10 mm), subxiphoid (5 mm), and right lateral subcostal margin (5 mm). Preliminary evacuation of empyematous gallbladder was performed by a percutaneous 21-gauge needle (). A fundus first approach was elected because of the severe inflammation of tissues surrounding the gallbladder and its hilum. The procedure lasted 45 minutes with repeated use of bipolar energy to control bleeding from the gallbladder bed. After removal of the gallbladder, thorough inspection of the hepatic bed was made and a little bile leak was identified from a duct of Luschka 1 cm away from the gallbladder hilum (). Direct suture with 5/0 PDS was attempted first but failed because of the poor quality of the inflamed hepatic tissue. In order to avoid any deeper suture that would involve major hepatic vessels due to the proximity with the hepatic hilum, an alternative technique was chosen. We inserted a QuickClip Pro® clip (Olympus Medical Systems Corp., Tokyo, Japan) through the subxiphoid trocar. This endoscopic device was directed by means of a Johann clamp inserted through the right subcostal trocar to securely close the duct of Luschka (). An abdominal drainage was left in place for 24 hours, and the patient was discharged on the second postoperative day.
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pmc-6311779-1
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A 77-year-old woman with a history of type 1 diabetes presented to the endocrinology clinic complaining of lightheadedness for several weeks. That morning, she experienced syncope and fell to the ground, striking her head. There were no episodes of severe or symptomatic hypoglycemia at home. She was directed to the emergency room, where a head CT revealed no evidence of hemorrhage and an electrocardiogram showed sinus tachycardia. Blood glucose was 34 mg/dL, so she was treated with intravenous dextrose, 25 grams. The patient was admitted to the telemetry floor. Over the subsequent 12 hours, blood glucose was monitored closely and remained between 179 and 303 mg/dL. She was treated with insulin glargine 24 units and insulin lispro 4 units TID with meals. Additional medications included enoxaparin prophylaxis, ezetimibe, fluoxetine, levothyroxine, lisinopril, potassium chloride, and pravastatin. With elevated blood glucose, she was treated with an additional dose of insulin lispro 5 units. The telemetry monitor demonstrated several 6- to 9-second episodes of asystole, with intact P waves. She was transferred to the medical intensive care unit for atrioventricular block and started on an isoproterenol drip. Initial laboratory studies were notable for glucose of 297 mg/dL but otherwise normal. Four hours later, bedside blood glucose measured glucose >600 mg/dL (see ). Repeat laboratory data showed sodium 99 mmol/L, bicarbonate 11 mmol/L, anion gap 20, and glucose 1,713 mg/dL. Glycohemoglobin was 7.5%. Thyroid stimulating hormone was normal. The patient was started on an insulin drip for diabetic ketoacidosis. The isoproterenol was discontinued, and a pacemaker was placed. One hour after the discontinuation of isoproterenol, laboratory studies showed sodium 138 mmol/L, potassium 3.9 mmol/L, serum bicarbonate 17 mmol/L, chloride 103 mmol/L, and glucose 510 mg/dL. Venous blood gas revealed pH 7.19, pCO2 44 mmHg, and bicarb 16 mmol/L. Five hours after the discontinuation of isoproterenol, the diabetic ketoacidosis resolved.
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pmc-6311782-1
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We report the case of a 66-year-old man who was referred to us in January 2017 because of leukocytosis in a routine blood count. The patient was asymptomatic. On examination, there was no palpable lymphadenopathy, splenomegaly, or hepatomegaly.
Initial white blood cell (WBC) count was 36.7 × 109/L, hemoglobin level 14.7 g/dl, and platelet count 600 × 109/L. Peripheral blood (PB) examination showed leukocytosis with neutrophilia, metamyelocytes and myelocytes, basophilia, and no blasts. No eosinophilia and dysplasia were noted. LDH was 329 U/L (normal reference values 120–246 U/L).
A bone marrow (BM) aspirate was hypercellular with myeloid hyperplasia; myeloid/erythroid ratio was increased to 9 : 1; blast count was 0.5% per nucleated marrow cells; and mild eosinophilia was evident. BM cytogenetics showed a 46,XY,t(8;22)(p11;q11)[19]/46,XY[1]. Fluorescence in situ hybridization (FISH) with LSI FGFR1 (8p11) Dual Color Break Apart (Abbott) showed the split of one of the two fusion signals indicating a chromosome breakage in the FGFR1 locus in 90% of 200 cells analyzed ().
BCR-FGFR1 reverse-transcriptase polymerase chain reaction was not possible to carry out.
The patient was initially managed with hydroxyurea. He was offered an hematopoietic stem-cell transplantation considering the poor prognosis of patients with t(8;22)(p11.2;q11.2). A new BM aspirate was performed 6 weeks later due to anemia which confirmed the diagnosis. Cytogenetic analysis confirmed the presence of t(8;22) as the sole aberration in all 20 metaphases analyzed.
Four months later, the patient underwent an allogeneic HSCT from an HLA-haploidentical relative (haplo-HSCT). A nonmyeloablative conditioning regimen was used (cyclophosphamide, busulfan, and fludarabine). Five × 106/kg CD34 cells were infused. Initial transplant course was unremarkable. Time to neutrophils >0.5 × 109/L was 17 days, and time to platelets >20 × 109/L was 20 days. No signs or symptoms of graft-versus-host disease (GVHD) were noted.
BM exams were performed regularly after HSCT. Cytogenetic remission as well as peripheral blood full-donor chimerism was documented from day 30. At the time of this writing (more than 8 months from HSCT), the patient remained clinically well without evidence of GVHD and in cytogenetic complete remission.
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pmc-6311783-1
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A 54-year-old male with a history of probable neurosarcoidosis, lymphocytic leptomeningitis, seizures, cirrhosis, and possible ethanol use disorder presented with encephalopathy, hypoxia, and several weeks of reported intermittent fevers. For the treatment of neurosarcoidosis, he was taking mycophenolate 1000 mg orally twice a day and last received an infliximab infusion the month prior to presentation.
Approximately seventeen months prior to presentation, the patient underwent extensive investigation for ataxia, near syncope, and encephalopathy, during which he received empiric treatment for encephalitis with corticosteroids, although herpes simplex virus studies were negative. Magnetic resonance imaging of the brain and spine from the cervical spinal cord to the lumbar spinal cord found leptomeningeal enhancement. Cerebral spinal fluid (CSF) found 24 white blood cells/mm3 (reference range 0–5 cells/mm3) with 83% lymphocytes (reference range 0–60%), 8 red blood cells/mm3 (reference range 0–0 cells/mm3), glucose of 35 mg/dL (reference range 40–70 mg/dL), protein of 247.6 mg/dL (reference range 15–45 mg/dL), and no oligoclonal bands. Biopsies of the brain and meninges found leptomeningeal fibrosis with prominent arachnoid cap cells. Chest imaging and fluorodeoxyglucose-positron emission tomography found nonspecific pulmonary nodules and hilar lymphadenopathy. Additional unremarkable studies included bone marrow biopsies, lung biopsies, and sinus biopsies. No infectious pathogens, including Histoplasma, or neoplastic processes were identified.
Eleven months prior to presentation, the patient presented with encephalopathy. He was thought to have lymphocytic leptomeningitis. Serum and CSF angiotensin-converting enzymes (ACE) were normal. CSF studies found 21 white blood cells/mm3 (no reference range) with 91% lymphocytes (no reference range), 1 red blood cell/mm3 (no reference range), glucose of 39 mg/dL (50–70 mg/dL), and protein of 188 mg/dL (15–45 mg/dL). Investigations for infectious pathogens, including serum and CSF fungal studies such as for histoplasmosis, and neoplastic processes were negative. He received intravenous immunoglobulins and corticosteroids for an unclear autoimmune disease. A month later, his neurology providers thought his symptoms and studies were consistent with probable neurosarcoidosis and proceeded with treatment using mycophenolate and infliximab. Six months prior to presentation, he developed keratitis and uveitis.
Vital signs at presentation were temperature of 36.4°C, blood pressure of 80 mmHg/52 mmHg, heart rate of 93 beats per minute, respiratory rate of 24 breaths per minute, and oxygen saturation of 91% on 10 liters per minute of supplemental oxygen. Conventional chest radiography () found a diffuse miliary pattern, which was also identified on subsequent computed tomography of the chest. CSF studies found 1 white blood cell/mm3 (no reference range) with 95% lymphocytes (no reference range), 1 red blood cell/mm3 (no reference range), glucose of 28 mg/dL (50–70 mg/dL), and protein of 53 mg/dL (15–45 mg/dL).
The patient received empiric vancomycin, piperacillin/tazobactam, and amphotericin for possible bacterial and fungal infections. He underwent endotracheal intubation for acute hypoxic respiratory failure and was extubated approximately one week later. Urine, serum, and CSF antigen studies were positive for histoplasmosis and blastomycosis, but the positive studies for blastomycosis were thought to be secondary to cross-reactivity. Respiratory culture obtained via bronchoscopy grew Histoplasma capsulatum. Fungal blood culture grew Histoplasma capsulatum. Bone marrow biopsy, obtained after the administration of antibacterial and antifungal agents, found hemophagocytosis that was thought to be consistent with the diagnosis of disseminated histoplasmosis, although the bone marrow culture had no growth of pathogens. For treatment of disseminated histoplasmosis, he completed a course of amphotericin, was briefly on itraconazole, and was transitioned to voriconazole, on which he was eventually discharged after a month-long hospitalization. Pneumocystis jirovecii polymerase chain reaction study of the bronchoalveolar lavage was positive for which he received a complete course of trimethoprim-sulfamethoxazole, although suspicion for pneumocystis pneumonia was low. The patient's hospital course was complicated by acute kidney injury, aspiration pneumonia, and Pseudomonas aeruginosa pneumonia.
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pmc-6311793-1
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A 73-year-old female with a past medical history of hypertension, hyperlipidemia, insulin-dependent diabetes mellitus, and coronary artery disease was admitted for an elective percutaneous coronary intervention (PCI) of a lesion detected in the right coronary artery. The patient had old stents to the mid-right coronary artery and mid-left anterior descending artery, and a stent in the mid-left circumflex artery that was deployed three weeks prior to this admission. On the day of the planned PCI, shortly after right femoral artery cannulation, the patient developed a sudden complete heart block. Atropine was immediately administered, and a temporary pacemaker was inserted. Subsequently, the patient developed a supraventricular tachycardia (SVT) with aberrancy. IV adenosine was given, and the rhythm changed to sinus tachycardia. Concomitantly, the patient developed acute pulmonary edema and became hypotensive and hypoxic. She was intubated, started on mechanical ventilation, and vasopressors were administered to maintain her blood pressure. A coronary angiogram showed patent left and right coronary arteries, unchanged when compared to the previous angiogram (Figures and ). An echocardiogram performed in the cardiac catheterization lab revealed global hypokinesis of the left and right ventricles, with severe left ventricular systolic dysfunction (EF < 20%) (Videos and ). Following an insertion of an intra-aortic balloon pump, the patient was transferred to the CICU. A repeat echocardiogram in the CICU two hours later revealed a classical echocardiographic presentation of Takotsubo syndrome (Videos and ). By the next morning, the patient's hemodynamic status significantly improved, the balloon pump was removed, and vasopressors were discontinued. Another echocardiogram was performed 24 hours after the event occurred and revealed a marked improvement of the left ventricular function (EF 60%), with complete resolution of apical and septal wall motion abnormalities (Videos and ). Three days after the event, the patient was successfully discharged. At a two-month follow-up visit, the patient was completely asymptomatic.
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pmc-6311803-1
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Our patient is a 54-year-old Caucasian male with a history of cardiac and pulmonary sarcoidosis, hypertension, premature ventricular contractions (PVCs), and obesity who presented with acute onset right hemianopsia, memory recall difficulty, and alexia without agraphia. He was in his normal state of health and doing yard work when the symptoms began.
In the past year, incidental PVCs were found on 12-lead electrocardiogram (ECG) during a preoperative evaluation for dental work. Holter monitoring revealed a 12% PVC burden over 24 hours, indicating an indeterminate degree of ventricular dysfunction. Cardiac evaluation of the PVCs included transthoracic echocardiogram which revealed hypokinesis of the left inferior ventricular wall with an ejection fraction of 35%. Cardiac catheterization for investigation of structural blockages of coronary vessels yielded no significant CAD.
These findings were suspicious for an infiltrative process. This hypothesis was supported by cardiac MRI showing sarcoid infiltrates on T2-weighted images and by discovery of noncaseating granulomas on pulmonary node biopsy. He was diagnosed with cardiac sarcoidosis three months after initial presentation. During this time, he showed no clinical symptoms of systemic sarcoidosis or heart failure. An implantable cardioverter defibrillator was placed for primary prevention of arrhythmias secondary to cardiac sarcoid. He was doing well for one year until he presented with stroke symptoms.
Our patient endorsed decreased vision on the right and described the words on his lawn mower being visible but not readable. He also acknowledged trouble with recalling names and specific events.
Upon examination, our patient demonstrated normal speech and language. He was asked to write a simple sentence and performed the task without difficulty. When asked to read the sentence, he was unable to do so, representing alexia without agraphia. He showed right homonymous hemianopia. The remainder of the physical exam was normal.
At admission, initial computed tomography (CT) scan was negative. Subsequent brain magnetic resonance imaging (MRI) and magnetic resonance angiogram (MRA) confirmed a left posterior cerebral artery (PCA) infarction (). MRA of the neck was unremarkable. The stroke was suspected to be cardioembolic in origin due the PVC burden and reduced ejection fraction of 35% promoting possible thrombus formation. Transesophageal echocardiogram revealed no thrombus or patent foramen ovale (PFO) and supported the previous finding of hypokinesis of left inferolateral ventricular wall (). Hypercoagulable workup was nonrevealing. There was no family history of sarcoidosis or early age stroke.
By the time of discharge, our patient's visual symptoms returned to baseline and he was given high dose aspirin and atorvastatin for secondary stroke prophylaxis. Cellcept and prednisone were prescribed for management of sarcoidosis. A LINQ device was placed for continuous ECG monitoring. Lisinopril and metoprolol were maintained for pressure and rhythm control.
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pmc-6311804-1
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A 64-year-old male with Diffuse Large B-Cell Non-Hodgkin's Lymphoma presented with one week of left-sided headache and right anterior calf pain, which worsened with walking and improved with rest. He also described low-grade fever and fatigue.
His past medical history was significant for Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma, previously treated with Rituximab. However, within the past two years, he gradually developed breathlessness and was found to have hilar lymphadenopathy. Further work-up had led to a diagnosis of Diffuse Large B-Cell Lymphoma. This had initially been treated with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (RCHOP) chemotherapy. He progressed approximately one year later with mediastinal lymphadenopathy. At this point, he was considered a candidate for high-dose therapy with stem cell transplant if induced into remission and, with this intention, had started salvage chemotherapy with Rituximab/Gemcitabine/Cisplatin/Dexamethasone. A week after starting this chemotherapy regimen, he developed the headache and claudication that led to this hospitalization.
He did not have any other past medical problems. There was no history of previous cardiovascular disease and no family history of premature cardiovascular disease. He was an ex-smoker and did not have substance abuse issues.
On examination, he had normal cardiovascular, neurological, pulmonary, and gastrointestinal examination. He did, however, have an absent right dorsalis pedis pulse.
Initial Computed Tomography (CT) Scan of the head and Duplex Scan of the leg were normal. His Magnetic Resonance Imaging (MRI)/Magnetic Resonance Angiography (MRA) Brain revealed no acute stroke and no intracranial atherosclerosis. Within twenty-four hours of hospital admission, he developed a visual defect in his left eye. CT angiogram of the head and neck was done and revealed occlusion of his left internal carotid artery, poor opacification of the left ophthalmic artery, and the presence of good collateral flow from the left posterior cerebral artery and the anterior communicating artery (Figures and ). There was no evidence of atherosclerosis elsewhere. Headache is an unusual symptom of acute internal cerebral artery occlusion, but dissection and vasculitis were excluded based on the CT angiogram of the head and neck.
An angiogram of the right leg revealed acute occlusion of the distal popliteal artery ().
Given the absence of stroke and the presence of good collateral flow in the brain, it was initially unclear whether the occlusions of his left carotid artery and right popliteal artery were acute or chronic.
Cardioembolism was excluded by a normal transthoracic echocardiogram, and telemetry monitoring did not reveal atrial fibrillation.
The differential diagnosis for these arterial thromboembolic events included acute disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura (TTP), and antiphospholipid antibody syndrome. Laboratory results and peripheral blood smear excluded these conditions.
Because of the visual defect in the left eye, the ophthalmologist was called and found the patient to have a left ophthalmic artery occlusion, embolic in nature. With new-onset vision loss secondary to embolization from the left carotid artery thrombus and the acute nature of all his symptoms, the left carotid artery thrombosis was also favored to be acute. After review of medical literature, we discussed whether Cisplatin/Gemcitabine had any role to play in the pathogenesis of his acute arterial thromboembolic events.
Initial management with antiplatelet and anticoagulant therapy had to be delayed because of the thrombocytopenia (25,000/mcl) he was experiencing because of his recent chemotherapy. After platelet transfusions to treat his thrombocytopenia, he underwent intra-arterial Tissue Plasminogen Activator (TPA) injection by Vascular Surgery to the right popliteal artery.
As his platelet count increased, he was initiated on Low Molecular Weight Heparin treatment and discharged home. His left vision gradually recovered with time.
Moving forward, a decision was made to avoid the thrombogenic potential of Gemcitabine and Cisplatin. His chemotherapy regimen was changed to RICE (Rituximab, Ifosfamide, Carboplatin, Etoposide).
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pmc-6311807-1
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A previously well 37-year-old woman presented to the outside hospital following a near-syncopal episode. Initial workup included a computed tomography (CT) of the abdomen and pelvis, which revealed massive hemoperitoneum secondary to splenic injury. The patient denied any history of trauma, and no etiology of her splenic injury was discovered. She received an immediate urgent visceral angiography which included a selective angiography of the spleen. Angiography did not reveal any areas of active bleeding within the abdomen including from the spleen itself; therefore, embolization was not pursued. The patient was admitted to the intensive care unit where she underwent scrupulous monitoring. She continued to have tachycardia with an acute drop in her hemoglobin; hence, she was taken emergently to the operating room for exploratory laparotomy and splenectomy. The anatomopathological analysis of the spleen showed a 142 g ruptured spleen which measured 10.5 × 8.1 × 2.5 cm. On the anterior surface, was an area of rupture measuring 7.5 × 5.0 cm, which was surrounded by hemorrhage. The capsule was peeled back from this area. On the posterior aspect of the spleen, was an area of disruption measuring 5.0 × 2.2 × 0.1 cm, which was also surrounded by hemorrhage. The remaining capsule was lavender and smooth. The spleen was serially sectioned to reveal beefy red, smooth parenchyma with no gross lesions. Lymph nodes were not identified within the hilum. No gross lesions were identified. The histopathologic examination showed no abnormality except capsular rupture (). She recovered well postoperatively and appeared improved at the time of discharge.
Two months later, the patient presented to our hospital with complaints of acute, severe, diffuse abdominal and low back pain. She had tachycardia while the other vital signs were normal. Laboratory studies revealed a hemoglobin of 10.5 g/dL, hematocrit of 33.9%, neutrophilia of 13.2 × 109/L, and thrombocytosis of 2239 × 109/L. CT abdomen with contrast revealed portal, mesenteric, and splenic vein thromboses. She denied any smoking history, had no family history of thrombophilia, and was not taking oral contraceptives. Thrombophilia workup (Factor V Leiden mutation and prothrombin gene mutations, protein C, protein S, antithrombin III, homocysteine levels, and antiphospholipid antibodies) was unremarkable. The erythropoietin level was high at 30 mIU/ml (normal range 2.6 to 18.5 mIU/ml). Other causes of reactive thrombocytosis, including infection, inflammation, trauma, and acute blood loss, were not identified. Bone marrow biopsy revealed hypercellularity (60% for age) with a marked increase in enlarged and mature hyperlobulated megakaryocytes, compatible with essential thrombocythemia (ET) (). There was no abnormality seen in granulocytic or erythroid precursors; both showed adequate number with normal maturation. Iron stores were adequate, and there was no evidence of fibrosis.
Another independent pathologist reviewed the bone marrow biopsy and confirmed the initial findings. The patient's cytogenetic profile showed normal female karyotype, 46, XX. BCR-ABL, JAK2 V617F, CALR (not specified to type 1 or 2), and MPL W515L/K gene mutations were negative. The patient was diagnosed with essential thrombocythemia [].
The patient received one urgent therapeutic platelet apheresis without complications, which resulted in the temporary removal of the majority of platelets []. Low-dose aspirin, low molecular weight heparin, and hydroxyurea 1000 mg daily were initiated. However, her platelet count continued to increase despite increasing hydroxyurea dose to 1500 mg daily; therefore, anagrelide 0.5 mg PO BID was added. At the time of discharge, the patient was asymptomatic and platelet count had decreased to 664 × 109/L. Due to intolerance, the anagrelide was discontinued on day 75. Six months later, hydroxyurea dose was decreased to 1000 mg daily, and she remains on this dose. At the time of this report, the patient has an ongoing positive response to treatment and platelet count has further decreased to 445 × 109/L ().
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pmc-6311816-1
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A 48-year-old male presented to the emergency room for recurrent syncope. He became acutely unresponsive while in the emergency room. His pupils became fixed and dilated bilaterally. Emergent computed tomography (CT) of the head revealed a ventricular colloid cyst with hydrocephalus and uncal herniation as shown in Figures and . Emergent bedside bilateral external ventricular drains were placed in the emergency room and the patient was subsequently intubated for airway protection. He was noted to be intermittently apneic and bradypnic on mechanical ventilation. The low minute ventilation persisted after liberation from mechanical ventilation. This was monitored with noninvasive end-tidal carbon dioxide detection and arterial blood gas sampling. The transient ACHS was managed with bilevel NIPPV intermittently, as needed for hypercapnia during wakefulness and continuously through sleep. The hypoventilation resolved after three to four days. Arterial blood gas sampling at that time revealed a PaCO2 of 35 mm Hg. NIPPV was discontinued and the patient made a full functional neurologic recovery. He underwent a successful transcallosal resection of the colloid cyst.
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